May 2020 – Page 151 – 1stOncology™: Cancer Intelligence Service

Merck’s KEYTRUDA® (pembrolizumab) Superior to Brentuximab Vedotin (BV), a Standard of Care, in Patients With Classical Hodgkin Lymphoma (cHL) in Head-to-Head Phase 3 Trial

On May 13, 2020 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported the first presentation of results from KEYNOTE-204, a Phase 3 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) (Press release, Merck & Co, MAY 13, 2020, View Source [SID1234557917]). In this pivotal study, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), one of the dual primary endpoints. KEYTRUDA reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88; p=0.00271]) and showed a median PFS of 13.2 months compared with 8.3 months for patients treated with brentuximab vedotin (BV), a current standard of care in this patient population. As previously announced, KEYNOTE-204 serves as the confirmatory trial for the KEYTRUDA accelerated approval hematology indications and the company plans to submit these data to global regulatory authorities this year.

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"In this head-to-head study, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in progression-free survival when compared with brentuximab vedotin, reinforcing the benefit of KEYTRUDA in classical Hodgkin lymphoma," said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. "Merck is committed to researching innovative approaches for the treatment of blood cancers through our broad clinical program evaluating KEYTRUDA across multiple hematologic malignancies and our investigational Bruton’s tyrosine kinase inhibitor MK-1026, which we recently added to our pipeline through our acquisition of ArQule."

"These data are particularly meaningful since approximately 15 to 20% of patients with classical Hodgkin lymphoma, the most common type of Hodgkin lymphoma, generally do not achieve remission following first-line treatment," said Dr. John Kuruvilla, hematologist and associate professor of medicine at the Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada. "Data from KEYNOTE-204 show that KEYTRUDA monotherapy has the potential to change the current treatment paradigm for these patients who are generally young and face a poor prognosis when they do not achieve remission."

These results are being presented in an oral abstract session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #8005). As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline. Follow Merck on Twitter via @Merck and keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO20.

KEYNOTE-204 Study Design and Additional Data (Abstract #8005)
KEYNOTE-204 is a randomized, open-label, Phase 3 trial evaluating KEYTRUDA monotherapy versus BV for the treatment of patients with relapsed or refractory cHL (ClinicalTrials.gov, NCT02684292). The dual primary endpoints are PFS and overall survival (OS). Key secondary endpoints include objective response rate (ORR), complete response rate and safety. The study enrolled 304 patients, aged 18 years and older, who were randomized to receive either KEYTRUDA (200 mg intravenously on Day 1 of each three-week cycle for up to 35 cycles) or BV (1.8 mg/kg [maximum 180 mg per dose] intravenously on Day 1 of each three-week cycle for up to 35 cycles). Per the pre-specified analysis plan, the other dual primary endpoint of OS was not formally tested at this interim analysis. The study will continue to evaluate OS.

In this study, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in PFS (HR=0.65 [95% CI, 0.48-0.88; p=0.00271]) and showed a median PFS of 13.2 months compared with 8.3 months for patients treated with BV. The one-year PFS rate was 53.9% with KEYTRUDA versus 35.6% with BV. Additionally, the ORR was 65.6% with KEYTRUDA versus 54.2% with BV, with a complete response observed in 24.5% and 24.2% of patients, respectively; partial responses were observed in 41.1% and 30.1% of patients, respectively. Median duration of response was 20.7 months (range, 0.0+ to 33.2+) with KEYTRUDA versus 13.8 months with BV (range, 0.0+ to 33.9+).

The incidence of treatment-related adverse events (TRAEs) was similar with KEYTRUDA (74.3%) compared with BV (77.0%). Grade 3-5 TRAEs were lower in patients treated with KEYTRUDA (19.6%) compared with BV (25.0%). There was one treatment-related death with KEYTRUDA (pneumonia).

Merck Investor Event
Merck will hold a virtual investor event in conjunction with the ASCO (Free ASCO Whitepaper) Annual Meeting on Tuesday, June 2 at 2 p.m. ET. Details will be provided at a date closer to the event at View Source

Merck’s Blood Cancer Research Program
Merck is studying KEYTRUDA across hematologic malignancies through a broad clinical program, including three registrational trials in cHL and primary mediastinal large B-cell lymphoma (PMBCL), and more than 60 investigator-initiated studies across 15 tumors. In addition to KEYTRUDA, Merck is evaluating the oral Bruton’s tyrosine kinase inhibitor MK-1026 (formerly ARQ 531), which the company acquired in the recent acquisition of ArQule. MK-1026 is currently in a Phase 2 dose expansion study for the treatment of B-cell malignancies.

About Hodgkin Lymphoma
Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells, called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere – most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. Worldwide, there were approximately 80,000 new cases of Hodgkin lymphoma and more than 26,000 people died from the disease in 2018. In 2020, it is estimated that nearly 8,500 people will be diagnosed with Hodgkin lymphoma in the U.S. Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin lymphoma in developed countries.

About KEYTRUDA (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer
KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies
KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions
Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma
In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

Lactation
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use
There is limited experience in pediatric patients. In a trial, 40 pediatric patients (16 children aged 2 years to younger than 12 years and 24 adolescents aged 12 years to 18 years) with various cancers, including unapproved usages, were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34 patients (85%) receiving 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults; adverse reactions that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), increased transaminases (28%), and hyponatremia (18%).

Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

Bristol Myers Squibb and bluebird bio to Present Updated Positive Results from Pivotal KarMMa Study of Ide-cel in Relapsed and Refractory Multiple Myeloma Patients at ASCO20

On May 13, 2020 Bristol Myers Squibb (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) reported updated results from the pivotal, Phase 2 KarMMa study evaluating the efficacy and safety of the companies’ investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, idecabtagene vicleucel (ide-cel; bb2121), in patients with relapsed and refractory multiple myeloma (Press release, bluebird bio, MAY 13, 2020, View Source [SID1234557916]). These data will be shared in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program on May 29 at 8:00 AM ET.

In the study, 128 patients with heavily pretreated relapsed and refractory multiple myeloma who were exposed to at least three prior therapies and were refractory to their last regimen per the International Myeloma Working Group (IMWG) definition (no response to therapy or disease progressed within 60 days) were treated with ide-cel across target dose levels of 150-450 x 106 CAR+ T cells. Patients had a median of six prior regimens; 84% were refractory to all three classes of commonly used treatments including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and 94% were refractory to anti-CD38 antibodies. Median duration of follow-up was 13.3 months.

The overall response rate (ORR) was 73% across all dose levels, including 33% of patients who had a complete response (CR) or stringent CR (sCR). Median duration of response (DoR) was 10.7 months, with 19.0 month median DoR for patients who had a CR or sCR. Median progression-free survival (PFS) was 8.8 months, with 20.2 month median PFS for patients who had a CR or sCR. All patients who had CR or sCR and were evaluable for minimal residual disease (MRD), were MRD-negative. Clinically meaningful benefit was consistently observed across subgroups, and nearly all subgroups had an ORR of 50% or greater, including older and high-risk patients. The overall survival (OS) data continue to mature, with an estimated median OS of 19.4 months across all dose levels and 78% of patients alive at 12 months.1 Results support a favorable benefit-risk profile for ide-cel across the target dose levels of 150 to 450 × 106 CAR+ T cells.

Ide-cel Treated Population Across Dose Range*
Dose, x 106 PCAR+ T cells 150
(n=4) 300
(n=70) 450
(n=54) 150-450
(n=128)
ORR, n (%) 2 (50) 48 (69) 44 (82) 94 (73)
CR/sCR, n (%) 1 (25) 20 (29) 21 (39) 42 (33)
Median DoR, mo
Median DoR by best
response (CR/sCR), mo -†
-† 9.9
-†† 11.3
-†† 10.7
19.0
Median PFS, mo
Median PFS by best
response (CR/sCR), mo 2.8
-† 5.8
-†† 12.1
-†† 8.8
20.2
* Data have been updated following abstract publication
† Not reported due to small n
†† Data not reported

The most frequently reported adverse events (AEs) were cytopenia and cytokine release syndrome (CRS). Cytopenias were common and not dose related. Overall, CRS of any grade was reported in 84% (107/128) of patients. Grade 3 or higher CRS occurred in <6% (7/128) of patients, with one fatal CRS event. Investigator identified neurotoxicity events (iiNT) were reported in 18% (23/128) of patients, including Grade 3 iiNT reported in 3% (4/128) of patients. There were no Grade 4 or Grade 5 iiNT events reported.2

"We are very encouraged and excited by the depth and durability of responses seen with ide-cel in this first pivotal study of a CAR T cell therapy in multiple myeloma. Patients with relapsed and refractory multiple myeloma have decreased life expectancy, with no clear standard of care and limited responses to currently available treatment options, leaving them in critical need of new therapies," said Nikhil C. Munshi, M.D., presenting author, Associate Director, The Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, Boston, Massachusetts. "The hematology and oncology community looks forward to the potential application of ide-cel in future clinical practice."

"These longer-term results from the KarMMa study further demonstrate the clinical benefit of ide-cel and support its role as a potentially important therapeutic option for patients with triple-class exposed, relapsed and refractory multiple myeloma," said Kristen Hege, M.D., senior vice president, Hematology/Oncology and Cell Therapy, Early Clinical Development, Bristol Myers Squibb. "BMS and bluebird bio remain focused on improving outcomes in this population and bringing ide-cel to patients as quickly as possible."

"Patients in the KarMMa study reflect a very advanced and highly refractory population, so it is particularly gratifying that the results announced today from the pivotal KarMMa study, demonstrating deep and durable responses, underscore the potential of ide-cel as a meaningful new treatment option for these patients," said David Davidson, M.D., Chief Medical Officer, bluebird bio. "bluebird bio, together with our partners at Bristol Myers Squibb, understands the urgency to deliver new therapeutic options for patients living with relapsed and refractory multiple myeloma, and we are committed to bringing this potentially first-in-class BCMA-directed CAR T cell therapy to patients in need."

Ide-cel is not approved for any indication in any geography.

About Ide-cel

Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Bristol Myers Squibb and bluebird bio’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio.

About KarMMa3

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with relapsed and refractory multiple myeloma in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Demonstrated Statistically Significant Improvement in Progression-Free Survival Versus Chemotherapy in Certain Patients with Metastatic Triple-Negative Breast Cancer

On May 13, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported positive results from the Phase 3 KEYNOTE-355 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as first-line treatment in patients with metastatic triple-negative breast cancer (mTNBC) (Press release, Merck & Co, MAY 13, 2020, View Source [SID1234557915]). In patients whose tumors expressed PD-L1 with Combined Positive Score (CPS) ≥10, KEYTRUDA plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 35% (HR = 0.65 [95% CI, 0.49-0.86], p=0.0012) and improving PFS to a median of 9.7 months compared to 5.6 months for those receiving chemotherapy alone. In patients whose tumors expressed PD-L1 with CPS ≥1, KEYTRUDA plus chemotherapy improved PFS versus chemotherapy alone (median PFS = 7.6 months versus 5.6 months; HR = 0.74 [95% CI, 0.61-0.90], p=0.0014), however these results did not meet statistical significance. As previously announced, the trial will continue without changes to evaluate the other dual primary endpoint of overall survival (OS).

"The progression-free survival results observed in KEYNOTE-355 have the potential to impart real change for certain patients with metastatic triple-negative breast cancer in the first-line setting," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "Merck is committed to evaluating innovative treatment approaches, anchored by KEYTRUDA, across multiple settings and stages of breast cancer. We are encouraged by the positive results from the Phase 3 KEYNOTE-355 and neoadjuvant/adjuvant KEYNOTE-522 studies, which demonstrate the potential of KEYTRUDA in combination with chemotherapy for the treatment of triple-negative breast cancer."

"There is a significant need for treatment regimens that can help women with metastatic triple-negative breast cancer, an aggressive disease," said Dr. Javier Cortes, Head Breast Cancer program, IOB Institute of Oncology, Quironsalud Group. "The results of this study, demonstrate that if approved, KEYTRUDA in combination with chemotherapy may offer certain women a new option for first-line treatment."

These results are being presented as an oral abstract session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1000). As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline. Follow Merck on Twitter via @Merck and keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO20.

The KEYTRUDA breast cancer clinical development program encompasses several internal and external collaborative studies. In addition to KEYNOTE-355, in TNBC these include the ongoing registration-enabling studies KEYNOTE-242 and KEYNOTE-522.

KEYNOTE-355 Study Design and Additional Data (Abstract #1000)

KEYNOTE-355 is a randomized, double-blinded, Phase 3 trial (ClinicalTrials.gov, NCT02819518) evaluating KEYTRUDA in combination with one of three different chemotherapies compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or mTNBC that has not been previously treated with chemotherapy in the metastatic setting. The dual primary endpoints are PFS and OS in patients whose tumors expressed PD-L1 (CPS ≥1 and CPS ≥10) and in all participants (intention-to-treat [ITT] population). The secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety.

KEYNOTE-355 enrolled 847 patients who were randomized 2:1 to receive KEYTRUDA (200 mg every 3 weeks) plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel or gemcitabine/carboplatin); or placebo plus nab-paclitaxel, paclitaxel or gemcitabine/carboplatin. Among enrolled patients in each treatment group, approximately 75% had tumors expressing PD-L1 with CPS ≥1 (n = 425/566 for KEYTRUDA plus chemotherapy; n = 211/281 for chemotherapy alone) and approximately 38% had had tumors expressing PD-L1 with CPS ≥10 (n = 220/566 for KEYTRUDA plus chemotherapy; n = 103/281 for chemotherapy alone).

As of data cut-off for this interim analysis (December 11, 2019), median time from randomization to data cut-off was 25.9 months for KEYTRUDA plus chemotherapy and 26.3 months for chemotherapy alone. KEYTRUDA plus chemotherapy significantly improved PFS versus chemotherapy alone in patients whose tumors expressed PD-L1 with CPS ≥10 (HR = 0.65 [95% CI, 0.49-0.86], p=0.0012). In patients whose tumors expressed PD-L1 with CPS ≥1, statistical significance for KEYTRUDA plus chemotherapy was not met, but KEYTRUDA plus chemotherapy improved PFS in this patient population versus chemotherapy alone (median PFS = 7.6 months versus 5.6 months; HR = 0.74 [95% CI, 0.61-0.90], p=0.0014). PFS was tested using a hierarchical strategy, such that testing was first performed in patients whose tumors expressed PD-L1 with CPS ≥10, then in patients whose tumors expressed PD-L1 with CPS ≥1, with partial alpha from PFS in patients with CPS ≥10 transferred over, and finally in the ITT population. Thus, statistical significance was not tested in the ITT population (median PFS = 7.5 months for KEYTRUDA plus chemotherapy versus 5.6 months for chemotherapy alone; HR = 0.82 [0.69-0.97]).

Safety was consistent with the known profiles of each regimen, and no new safety signals were observed. Treatment-related adverse events (TRAEs) of any grade occurred in 96.3% of patients receiving KEYTRUDA plus chemotherapy (n=562) and 95.0% of patients receiving chemotherapy (n=281). Grade 3-5 TRAEs occurred in 68.1% of patients receiving KEYTRUDA plus chemotherapy and 66.9% of patients receiving chemotherapy. The most common Grade 3-5 TRAEs (occurring in ≥10% of patients) were neutropenia (29.7%), decreased neutrophil count (17.4%) and anemia (16.4%) for KEYTRUDA plus chemotherapy and neutropenia (29.9%), decreased neutrophil count (20.3%), and anemia (14.6%) for chemotherapy. TRAEs resulting in discontinuation of any treatment occurred in 18.1% of patients receiving KEYTRUDA plus chemotherapy and 11.0% of patients receiving chemotherapy. There were two treatment-related deaths in patients receiving KEYTRUDA plus chemotherapy.

Immune-mediated adverse events (AEs) of any grade occurred in 25.6% of patients receiving the KEYTRUDA plus chemotherapy and 6.0% of patients receiving chemotherapy. For patients receiving KEYTRUDA plus chemotherapy, the most common immune-mediated AE (occurring in ≥10% of patients) was hypothyroidism (15.5%). There were no immune-mediated AEs occurring in ≥10% of patients receiving chemotherapy.

Merck Investor Event

Merck will hold a virtual investor event in conjunction with the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting on Tuesday, June 2 at 2 p.m. ET. Details will be provided at a date closer to the event at View Source

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use

There is limited experience in pediatric patients. In a trial, 40 pediatric patients (16 children aged 2 years to younger than 12 years and 24 adolescents aged 12 years to 18 years) with various cancers, including unapproved usages, were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34 patients (85%) receiving 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults; adverse reactions that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), increased transaminases (28%), and hyponatremia (18%).

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

New Combination Data for Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Clinical Benefit in Stage III Non-Small Cell Lung Cancer (NSCLC) and Reinforce Long-Term Survival in Metastatic NSCLC

On May 13, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported positive results from two studies from the company’s leading lung cancer research program (Press release, Merck & Co, MAY 13, 2020, View Source [SID1234557914]). Initial results from the Phase 2 KEYNOTE-799 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus concurrent chemoradiation therapy (CCRT) demonstrated an objective response rate (ORR) of 67.0% in Cohort A (squamous and nonsquamous non-small cell lung cancer [NSCLC] patients who received paclitaxel plus carboplatin) and 56.6% in Cohort B (nonsquamous NSCLC patients who received cisplatin plus pemetrexed) in untreated patients with unresectable, locally advanced stage III NSCLC. Additionally, new and updated data from the final analysis of the pivotal Phase 3 KEYNOTE-189 trial showed that 45.7% of patients with metastatic nonsquamous NSCLC treated with KEYTRUDA in combination with chemotherapy were alive at two years versus 27.3% of patients treated with chemotherapy alone.

"KEYTRUDA has become a standard of care in metastatic non-small cell lung cancer based on the strength of clinical data showing a survival benefit as monotherapy or in combination with chemotherapy," said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. "New data from KEYNOTE-799 demonstrate the potential of KEYTRUDA plus concurrent chemoradiation therapy in earlier stages of lung cancer, while the long-term survival data from KEYNOTE-189 add to the strong body of evidence supporting the use of KEYTRUDA in combination with chemotherapy for appropriate patients with metastatic non-small cell lung cancer."

"Approximately 20-30% of patients with unresectable stage III non-small cell lung cancer have disease progression after initially receiving chemoradiation," said Salma K. Jabbour, radiation oncologist, professor, vice chair of clinical research, Rutgers Cancer Institute of New Jersey. "The encouraging results from KEYNOTE-799 demonstrate that combining KEYTRUDA with concurrent chemoradiation therapy has the potential to address a significant unmet medical need."

Merck is a leader in lung cancer, with an extensive clinical development program evaluating KEYTRUDA, in combination or as monotherapy, for the treatment of lung cancer across all stages of disease and lines of therapy in over 200 trials with more than 10,000 patients. In addition to KEYNOTE-799, Merck has initiated the Phase 3 KEYLYNK-012 study (ClinicalTrials.gov, NCT04380636), which will evaluate KEYTRUDA plus CCRT followed by one year of KEYTRUDA alone or in combination with LYNPARZA (olaparib) post-CCRT in patients with unresectable, locally advanced stage III NSCLC. KEYLYNK-012 is one of three new pivotal Phase 3 trials evaluating KEYTRUDA in combination with LYNPARZA for NSCLC. Additional studies include KEYLYNK-006 (nonsquamous patients; ClinicalTrials.gov, NCT03976323) and KEYLYNK-008 (squamous patients; ClinicalTrials.gov, NCT03976362), evaluating KEYTRUDA and maintenance LYNPARZA for the first-line treatment of metastatic NSCLC.

Results from KEYNOTE-799 (Abstract #9008) and KEYNOTE-189 (Abstract #9582) are being presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline. Follow Merck on Twitter via @Merck and keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO20.

First Presentation of Data from KEYNOTE-799 in Stage III NSCLC (Abstract #9008)

KEYNOTE-799 (ClinicalTrials.gov, NCT03631784) is a Phase 2, non-randomized, open-label study of 216 untreated patients with unresectable, locally advanced stage IIIA–C NSCLC designed to evaluate the efficacy of KEYTRUDA plus CCRT. All patients received KEYTRUDA, standard thoracic radiotherapy and investigator’s choice of two chemotherapy regimens. Cohort A included patients across NSCLC histologies who received paclitaxel plus carboplatin and Cohort B included only nonsquamous NSCLC patients who received cisplatin plus pemetrexed. Primary endpoints are ORR and rate of Grade ≥3 pneumonitis. Secondary endpoints include progression-free survival (PFS), overall survival (OS) and safety.

In all patients from Cohort A (n=112) and Cohort B (n=53) with a minimum of 15 weeks of follow-up, KEYTRUDA plus CCRT showed an ORR of 67.0% (90% CI, 58.9-74.3) and 56.6% (90% CI, 44.4-68.2) for Cohort A (2.7% complete response [CR]) and Cohort B (3.8% CR), respectively. The median duration of response (DOR) was not reached in either Cohort A (range, 1.6+ to 10.5+) or Cohort B (range, 1.7+ to 10.5+) as of data cutoff. Additionally, 91.1% and 100% of patients in Cohort A and B, respectively, had a response lasting six months or longer. In Cohort A, the six-month PFS rate was 81.4% and the six-month OS rate was 87.2%. In Cohort B, the six-month PFS rate was 85.2% and the six-month OS rate was 94.8%.

The incidence of adverse events (AEs) among patients who received KEYTRUDA plus CCRT was consistent with the established toxicity profiles of CCRT for stage III NSCLC and KEYTRUDA monotherapy. All-cause Grade ≥3 pneumonitis occurred in 8.0% (n=9) of patients in Cohort A and 5.5% (n=4) of patients in Cohort B; four deaths (Grade 5 pneumonitis) occurred in Cohort A. Observed rates of Grade ≥3 pneumonitis were within the expected range for immunotherapy combined with CCRT. The incidence of treatment-related Grades 3-5 AEs was 64.3% (n=72) in Cohort A and 41.1% (n=30) in Cohort B. Treatment-related AEs leading to discontinuation of any treatment component occurred in 28.6% (n=32) of patients in Cohort A and 12.3% (n=9) in Cohort B.

New Two-Year Survival Data from KEYNOTE-189 in Metastatic NSCLC (Abstract #9582)

New and updated data from the protocol-specified final analysis of KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) continue to show that KEYTRUDA in combination with chemotherapy maintained a sustained, long-term survival benefit over chemotherapy alone after 31.0 months of median follow-up. The pivotal Phase 3 KEYNOTE-189 trial evaluated KEYTRUDA in combination with pemetrexed (ALIMTA) and platinum (cisplatin or carboplatin) chemotherapy for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone in patients with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% (HR=0.56 [95% CI, 0.46-0.69]) compared with chemotherapy alone, with a median OS of 22.0 versus 10.6 months. The two-year OS rate was 45.7% for KEYTRUDA in combination with chemotherapy versus 27.3% with chemotherapy alone. KEYTRUDA in combination with chemotherapy also reduced the risk of disease progression or death by half (HR=0.49 [95% CI, 0.41-0.59]) compared with chemotherapy alone, with a median PFS of 9.0 versus 4.9 months. The two-year PFS rate was 22.0% for KEYTRUDA in combination with chemotherapy versus 3.4% for chemotherapy alone. The ORR was 48.3% for KEYTRUDA in combination with chemotherapy versus 19.9% for chemotherapy alone.

Among the 56 patients who completed two years of treatment with KEYTRUDA, the ORR was 85.7%. Median OS was not reached.

The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with metastatic NSCLC. Grades 3-5 AEs occurred in 72.1% of patients who received KEYTRUDA in combination with chemotherapy and 66.8% of patients who received chemotherapy alone. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of ALIMTA (pemetrexed).

Merck Investor Event

Merck will hold a virtual investor event in conjunction with the ASCO (Free ASCO Whitepaper) Annual Meeting on Tuesday, June 2 at 2 p.m. ET. Details will be provided at a date closer to the event at View Source

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. The five-year survival rate for patients diagnosed in the U.S. with NSCLC and SCLC is estimated to be 5% and 6%, respectively.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

Selected KEYTRUDA Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

Small Cell Lung Cancer

Head and Neck Squamous Cell Cancer

Classical Hodgkin Lymphoma

Primary Mediastinal Large B-Cell Lymphoma

Urothelial Carcinoma

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

Gastric Cancer

Esophageal Cancer

Cervical Cancer

Hepatocellular Carcinoma

Merkel Cell Carcinoma

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-Mediated Pneumonitis

Immune-Mediated Colitis

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

Hepatotoxicity in Combination With Axitinib

Immune-Mediated Endocrinopathies

Immune-Mediated Nephritis and Renal Dysfunction

Immune-Mediated Skin Reactions

Other Immune-Mediated Adverse Reactions

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Increased Mortality in Patients With Multiple Myeloma

Embryofetal Toxicity

Adverse Reactions

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use

Please see Prescribing Information for KEYTRUDA at View Source and Medication Guide for KEYTRUDA at View Source

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

Merck’s Focus on Cancer

AstraZeneca advances the science of cancer medicine with practice-changing data at the ASCO20 Virtual Scientific Program

On May 13, 2020 AstraZeneca reported that it will present ground-breaking new results across its broad portfolio of cancer medicines during the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, 29 to 31 May 2020 (Press release, AstraZeneca, MAY 13, 2020, View Source [SID1234557913]). AstraZeneca will present 98 abstracts, including 19 oral presentations with one plenary and 10 late-breakers.

Presentations will showcase the Company’s leadership in the treatment of early lung cancer with a late-breaking plenary presentation of the unprecedented results from the Phase III ADAURA trial for Tagrisso (osimertinib) in the adjuvant treatment of patients with Stage IB, II and IIIA epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Data from the DESTINY programme will highlight the transformative potential of Enhertu (trastuzumab deruxtecan) across HER2-driven tumours, including in lung, breast, gastric and colorectal cancers.

José Baselga, Executive Vice President, Oncology R&D, said: "AstraZeneca continues to deliver results with the goal of transforming clinical practice. Our science at ASCO (Free ASCO Whitepaper) this year shows the potential for treatment of early-stage EGFR-mutated lung cancer, where we aim to provide the hope of cure with Tagrisso; to rewrite the rules on the treatment of patients with HER2-positive tumours with Enhertu across a range of cancer settings; and to advance our next wave of pipeline medicines focused on treating patients earlier and overcoming resistance."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "One constant throughout these uncertain times is our unwavering commitment to changing the practice of medicine for patients living with cancer. Our new oncology medicines Tagrisso, Imfinzi, Lynparza, and Enhertu are demonstrating incredible momentum at ASCO (Free ASCO Whitepaper), building on their established benefits for patients by delivering powerful data in new settings and bending cancer survival curves. This year’s data at ASCO (Free ASCO Whitepaper) reinforce our belief that we can one day eliminate cancer as a cause of death."

Leadership in lung cancer across stages of disease

As AstraZeneca continues to advance lung cancer research and development from early to late-stage settings, the Company will present new data for Tagrisso, Imfinzi (durvalumab), Enhertu, and potential new medicine savolitinib. Beyond ADAURA, an oral presentation of the final analysis of the Phase III CASPIAN trial confirms the sustained, clinically meaningful overall survival (OS) benefit of Imfinzi for patients with extensive-stage small cell lung cancer (ES-SCLC). Another oral presentation reinforces the potential of Enhertu for patients with HER2-mutant NSCLC (see below). Results from a Phase II trial of savolitinib in patients with mesenchymal-epithelial transition (MET) exon 14 skipping mutations will also be presented.

Transforming treatment across HER2-driven cancers

AstraZeneca, in collaboration with Daiichi Sankyo Company, Limited (Daiichi Sankyo) will present new data from several trials highlighting the transformative potential of Enhertu, including detailed results from the Phase II DESTINY-Gastric01 trial which showed a statistically significant and clinically meaningful improvement in objective response rate and OS for patients with HER2-positive metastatic gastric cancer. Enhertu was recently granted Breakthrough Therapy Designation in the US for patients in this setting. Phase II data will also be presented for HER2-positive colorectal cancer and HER2-mutant NSCLC, two cancer settings for which there are currently no approved HER2-targeted medicines. Additionally, subgroup analyses from the Phase II DESTINY-Breast01 trial will reinforce the durable and consistent responses seen with Enhertu in HER2-positive metastatic breast cancer.

Advancing treatment in other cancer types with high unmet need

AstraZeneca will present data from several trials highlighting how the Company’s leading research is progressing treatment in other cancers where a high unmet medical need remains, including:

An oral presentation of results from Study 22 for the Imfinzi plus tremelimumab combination using a novel regimen in advanced liver cancer
Final OS results from the Phase III SOLO2 trial for Lynparza (olaparib) maintenance treatment in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in an oral presentation. Lynparza is developed and commercialised in collaboration with MSD (MSD: known as Merck & Co., Inc. inside the US and Canada)
Multiple trials underscoring the impressive profile of Calquence (acalabrutinib), including data from the Phase II ACE-CL-001 trial with more than four years of follow up. The presentations represent the most mature safety and efficacy data to date with Calquence monotherapy in patients with chronic lymphocytic leukaemia
Key AstraZeneca presentations during the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program
Lead author

Abstract title

Presentation details1

Immuno-Oncology

Paz-Ares, L

Durvalumab ± tremelimumab + platinum-etoposide in first-line ES-SCLC: Results from the Phase III CASPIAN study

Abstract #9002

Oral Abstract Session – Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Chen, Y

First-line durvalumab plus platinum-etoposide in ES-SCLC (CASPIAN): Impact of brain metastases on treatment patterns and outcomes

Abstract #9068

Poster #261

Poster Session – Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Naidoo, J

Non-pneumonitis immune-mediated adverse events with durvalumab in patients with unresectable, Stage III NSCLC (PACIFIC)

Abstract #9048

Poster #241

Poster Session – Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Kelley, RK

Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab in combination with durvalumab for patients with advanced hepatocellular carcinoma (Study 22)

Abstract #4508

Oral Abstract Session – Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary

Oh, Do-Youn

Phase II study assessing tolerability, efficacy and biomarkers for durvalumab ± tremelimumab and gemcitabine/cisplatin in chemo-naïve advanced biliary tract cancer

Abstract #4520
Poster #128

Poster Session – Gastrointestinal Cancer: Gastroesophageal, Pancreatic, and Hepatobiliary

Lim, E

A Phase I, open-label multi-center study to assess the safety, pharmacokinetics, and the preliminary antitumor activity of AZD4635 both as monotherapy and in combination in patients with advanced solid malignancies: results from prostate cancer patients

Abstract #5518
Poster #99

Poster Session – Genitourinary Cancer – Prostate, Testicular, and Penile

DNA damage response

Poveda, A

Final overall survival results from SOLO2: a Phase III trial assessing maintenance olaparib in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation

Abstract #6002

Oral Abstract Session – Gynecologic Cancer

Cadoo, K

Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study

Abstract #6013
Poster #184

Poster Discussion – Gynecologic Cancer

Lee, J

Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial

Abstract #6056
Poster #227

Poster Session – Gynecologic Cancer

Poveda, A

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated platinum-sensitive relapsed ovarian cancer patients: Phase IIIb OPINION interim analysis

Abstract #6057
Poster #228

Poster Session – Gynecologic Cancer

Liu, J

A Phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer

Abstract #6003

Oral Abstract Session – Gynecologic Cancer

Gelmon, K

Real-world clinical effectiveness and safety of olaparib monotherapy in HER2-negative gBRCA-mutated metastatic breast cancer: Phase IIIb LUCY interim analysis

Abstract #1087

Poster #172

Poster Session – Breast Cancer – Metastatic

Tumour drivers and resistance

Herbst, R

Osimertinib as adjuvant therapy in patients with Stage IB–IIIA EGFRm NSCLC after complete tumor resection: ADAURA

Abstract #LBA5

Plenary Session
Sunday 31 May, 1:00pm EDT

Lu, S

Phase II study of savolitinib in patients with pulmonary sarcomatoid carcinoma and other types of NSCLC harboring MET exon 14 skipping mutations

Abstract #9519

Poster #285

Poster Discussion – Lung Cancer – Non-Small Cell Metastatic

Choueiri, T

SAVOIR: A Phase III study of savolitinib vs. sunitinib in patients with MET-driven papillary renal cell carcinoma

Abstract #5002

Oral Abstract Session – Genitourinary Cancer – Kidney and Bladder

Julia, K

Concurrent osimertinib plus gefitinib for first-line treatment of EGFR-mutated NSCLC

Abstract # 9507

Oral Abstract Session – Lung Cancer- Non-Small Cell Metastatic

Piotrowska, Z

ECOG-ACRIN 5162: A Phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions

Abstract #9513

Poster #279

Poster Discussion – Lung Cancer – Non-Small Cell Metastatic

Hamilton, E

A Phase I dose escalation and expansion study of the next generation oral SERD AZD9833 in women with ER-positive, HER2-negative advanced breast cancer (SERENA-1)

Abstract #1024

Poster #109

Poster Discussion – Breast Cancer – Metastatic

Schmid, P

A Phase III trial of capivasertib and paclitaxel in first-line treatment of patients with metastatic triple-negative breast cancer (CAPItello290)

Abstract #TPS1109

Poster #194

Poster Session – Breast Cancer – Metastatic

Haematology

Ghia, P

Acalabrutinib vs Idelalisib plus Rituximab or Bendamustine plus Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia: ASCEND Final Results

Abstract #8015

Poster #348

Poster Discussion – Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Byrd, C

Acalabrutinib in Treatment-Naïve Chronic Lymphocytic Leukemia: Mature Results From Phase II Study Demonstrating Durable Remissions and Long-Term Tolerability

Abstract #8024

Poster #357

Poster Session – Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Furman, R

Safety of Acalabrutinib Monotherapy in Hematologic Malignancies: Pooled Analysis From Clinical Trials

Abstract #8064

Poster #397

Poster Session – Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Antibody drug conjugates

Smit, E

Trastuzumab deruxtecan in patients with HER2-mutated metastatic NSCLC: Interim results of DESTINY-Lung01

Abstract # 9504

Oral Abstract Session – Lung Cancer- Non-Small Cell Metastatic

Shitara, K

Trastuzumab deruxtecan in patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma: A randomized, Phase II, multicenter, open-label study (DESTINY-Gastric01)

Abstract #4513

Poster #121

Poster Session – Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary

Siena, S

A Phase II, multicenter, open-label study of trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer: DESTINY-CRC01

Abstract #4000

Oral Abstract Session – Gastrointestinal Cancer – Colorectal and Anal

Modi, S

Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis

Abstract #1036

Poster #121

Poster Session – Breast Cancer- Metastatic

1. Beginning Friday, 29 May 2020 8:00 AM EDT oral presentations, poster discussions and poster sessions will be available on demand for 180 days including video and slide presentations and discussant commentary.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

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Month: May 2020

Merck’s KEYTRUDA® (pembrolizumab) Superior to Brentuximab Vedotin (BV), a Standard of Care, in Patients With Classical Hodgkin Lymphoma (cHL) in Head-to-Head Phase 3 Trial

Bristol Myers Squibb and bluebird bio to Present Updated Positive Results from Pivotal KarMMa Study of Ide-cel in Relapsed and Refractory Multiple Myeloma Patients at ASCO20

Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Demonstrated Statistically Significant Improvement in Progression-Free Survival Versus Chemotherapy in Certain Patients with Metastatic Triple-Negative Breast Cancer

New Combination Data for Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Clinical Benefit in Stage III Non-Small Cell Lung Cancer (NSCLC) and Reinforce Long-Term Survival in Metastatic NSCLC

AstraZeneca advances the science of cancer medicine with practice-changing data at the ASCO20 Virtual Scientific Program