Myriad Genetics to Present Seven Studies at the 2017 American Society of Clinical Oncology Annual Meeting

On May 18, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that it will present results from seven studies at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting to be held June 2 to 6, 2016 in Chicago, Ill (Press release, Myriad Genetics, MAY 18, 2017, View Source [SID1234519220]). Abstracts of the Company’s presentations are currently available at: abstracts.asco.org

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“We look forward to presenting important new research at ASCO (Free ASCO Whitepaper) in collaboration with our academic partners, advancing personalized medicine in the field of oncology,” said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. “Our presentations will highlight advances in companion diagnostics, hereditary cancer risk assessment, and prediction of oncologic outcomes, all of which are designed to meaningfully improve clinical care for patients.”

A list of Myriad presentations at ASCO (Free ASCO Whitepaper) 2017 is below. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #ASCO17.

Title

Author Poster/Abstract Number

Day/Time Myriad Product

Podium Presentation

Evaluation of BRCA1/2 and homologous
recombination defects in ovarian cancer and
impact on clinical outcomes Melinda Yates Abstract 5511 Monday,
June 5,
2017: 8:00-
9:30 a.m.
CDT.
Room
E450ab

myChoice
HRD
Poster Discussion
Quantifying Gender Ascertainment Bias in
Hereditary Cancer Testing

Anthony Chen Abstract 6516
Poster Board
338 Monday,
June 5,
2017: 1:15-
4:45 p.m.
and 4:45-
6:00 p.m.
CDT. Myriad
myRisk
Poster Presentations
Expanded Yield of Multiplex Panel Testing in
Fully Accrued Prospective Trial

Performance of Mutation Risk Prediction
Models in a Racially Diverse Multi-Gene Panel
Testing Cohort

Gregory Idos Abstract 1525
Poster Board
183

Abstract 1523
Poster Board
181

Monday,
June 5,
2017: 1:15-
4:45 p.m.
CDT. Myriad
myRisk
Development and Validation of a Residual Risk
Score to Predict Breast Cancer Risk in
Unaffected Women Negative for Mutations on a
Multi-Gene Hereditary Cancer Panel

Elisha Hughes Abstract 1579
Poster Board
237 Monday,
June 5,
2017: 1:15-
4:45 p.m.
CDT. Myriad
myRisk
Safety of Multiplex Gene Testing for Inherited
Cancer Risk in a Fully Accrued Prospective
Trial Allison Kurian Abstract 1576
Poster Board
234 Monday,
June 5,
2017: 1:15-
4:45 p.m.
CDT.

Myriad
myRisk
Multi-Gene Hereditary Cancer Testing among
Men with Breast Cancer Krystal Brown Abstract 1532
Poster Board
190 Monday,
June 5,
2017: 1:15-
4:45 p.m. CDT. Myriad
myR

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder Cancer

On May 18, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved two new indications for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer (Press release, Merck & Co, MAY 18, 2017, View Source [SID1234519216]).

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In the first-line setting, KEYTRUDA is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. 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 the confirmatory trials. In the second-line setting, KEYTRUDA is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma 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 approved for use in these indications at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Immune-mediated adverse reactions occurred with KEYTRUDA including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of infusion-related reactions; for Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA (pembrolizumab). Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Female patients of reproductive potential should be advised of the potential hazard to a fetus. For more information regarding immune-mediated and infusion-related adverse reactions and use in pregnancy, see "Selected Important Safety Information" below.

"KEYTRUDA is now available for use as a first-line treatment option for patients with advanced urothelial bladder cancer who are not eligible for the standard of care, cisplatin-based chemotherapy," said Dean F. Bajorin, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. "With the second-line indication, KEYTRUDA also provides a new option for patients with advanced urothelial bladder cancer – and is the only anti-PD-1 therapy to show an overall survival benefit versus chemotherapy in a phase 3 study."

"These two indications mark important additions to the growing list of tumors and treatment settings for which KEYTRUDA is now approved. This FDA approval further demonstrates Merck’s commitment to help improve the lives of patients with many types of advanced cancer," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.

The KEYTRUDA clinical development program includes more than 30 tumor types in nearly 500 clinical trials, including more than 250 trials that combine KEYTRUDA with other cancer treatments. Currently, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 29 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.

Data Supporting First-Line Cisplatin-Ineligible Approval

The first-line approval is based on data from a multicenter, open-label, single-arm trial, KEYNOTE-052, investigating KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. Patients with autoimmune disease or medical conditions that required systemic corticosteroids or other immunosuppressive medication were excluded from the trial. Patients received KEYTRUDA at a dose of 200 mg every three weeks until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The major efficacy outcome measures were objective response rate (ORR), according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by independent radiology review, and duration of response.

The efficacy analysis showed an ORR of 29 percent (95% CI: 24, 34), with a complete response rate of 7 percent and a partial response rate of 22 percent. The median duration of response had not been reached (range: 1.4+ to 17.8+ months). The median follow-up time was 7.8 months.

In KEYNOTE-052, KEYTRUDA (pembrolizumab) was discontinued due to adverse reactions in 11 percent of patients. The most common adverse reactions (in ≥ 20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%) and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and three patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA occurred in 22 percent of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42 percent of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

Data Supporting Second-Line Post-Platinum Failure Approval

The second-line approval is based on data from a multicenter, randomized, active-controlled trial, KEYNOTE-045, investigating KEYTRUDA in patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients with autoimmune disease or a medical condition that required immunosuppression were excluded from the trial. Patients were randomized to receive either KEYTRUDA 200 mg every three weeks (n=270) or investigator’s choice of any of the following chemotherapy regimens, all given intravenously, every three weeks (n=272): paclitaxel 175 mg/m2 (n=84), docetaxel 75 mg/m2 (n=84), or vinflunine 320 mg/m2 (n=87). Treatment continued until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The major efficacy outcomes were overall survival (OS) and progression-free survival (PFS), as assessed by a blinded independent central review (BICR) per RECIST 1.1; additional efficacy outcome measures were ORR, as assessed by BICR per RECIST 1.1, and duration of response.

KEYTRUDA demonstrated superior OS compared to chemotherapy. Findings demonstrated that KEYTRUDA resulted in a 27 percent reduction in the risk of death compared to chemotherapy – with 155 events (57%) observed in the KEYTRUDA arm, compared to 179 events (66%) in the chemotherapy arm (HR, 0.73 [95% CI: 0.59, 0.91], p=0.004); the median OS was 10.3 months (95% CI: 8.0, 11.8) in the KEYTRUDA arm, compared to 7.4 months (95% CI: 6.1, 8.3) in the chemotherapy arm. In October 2016, the study was stopped early at the recommendation of an independent Data Monitoring Committee following an interim analysis that showed KEYTRUDA met the superiority thresholds for OS in the overall study population.

There was no statistically significant difference between KEYTRUDA (pembrolizumab) and chemotherapy with respect to PFS. There were 218 events (81%) observed in the KEYTRUDA arm, compared to 219 events (81%) in the chemotherapy arm (HR, 0.98 [95% CI: 0.81, 1.19], p=0.833). The median PFS was 2.1 months (95% CI: 2.0, 2.2) in the KEYTRUDA arm, compared to 3.3 months (95% CI: 2.3, 3.5) in the chemotherapy arm.

Analysis of the ORR endpoint showed a statistically significant improvement with KEYTRUDA, as compared to chemotherapy. The ORR was 21 percent (95% CI: 16, 27) in the KEYTRUDA arm (with a complete response rate of 7 percent and a partial response rate of 14 percent), compared to 11 percent (95% CI: 8, 16) in the chemotherapy arm (with a complete response rate of 3 percent and a partial response rate of 8 percent) (p=0.002). The median duration of response for patients treated with KEYTRUDA had not yet been reached (range: 1.6+ to 15.6+ months), compared to 4.3 months (range: 1.4+ to 15.4+ months) in the chemotherapy arm. The median follow-up time for this trial was 9.0 months.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in eight percent of patients. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20 percent of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (≥20%) in patients who received KEYTRUDA versus those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%) and rash (20% vs 13%). Serious adverse reactions occurred in 39 percent of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.

About KEYTRUDA (pembrolizumab) Injection

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.

Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with nearly 500 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.

KEYTRUDA (pembrolizumab) is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single-dose vial.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also 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.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA 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. 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. In HNSCC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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 three 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. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. 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 the confirmatory trials.

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

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. 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.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

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

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. 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%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.

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

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. 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. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Based on its mechanism of action, KEYTRUDA (pembrolizumab) can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11 percent of 370 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reactions (in ≥ 20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%) and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42 percent of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8 percent 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%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (≥20%) in patients who received KEYTRUDA versus those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%) and rash (20% vs 13%). Serious adverse reactions occurred in 39 percent of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes nearly 500 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

Helsinn Group and MEI Pharma Announce Upcoming Presentations of Gene Mutation and Clinical Response Data from Phase II Study of Pracinostat and Azacitidine in Acute Myeloid Leukemia

On May 18, 2017 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that data on the correlation between gene mutation clearance and clinical response from a Phase II clinical study of Pracinostat and azacitidine in older patients with acute myeloid leukemia (AML) have been accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Monday, June 5, 2017, and the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Madrid on Friday, June 23, 2017 (Press release, MEI Pharma, MAY 18, 2017, View Source [SID1234519214]). Abstracts of the presentations are now available at abstracts.asco.org and www.ehaweb.org.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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ASCO
Title: Correlation between Mutation Clearance and Clinical Response in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine and Pracinostat
Abstract Number: 7034
Session Title: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes and Allotransplant
Date and Time: Monday, June 5, 2017, 8:00 a.m. – 11:30 a.m. CDT (9:00 a.m. – 12:30 p.m. EDT)

EHA
Title: Treatment of Pracinostat and Azacitidine in Elderly Patients with Acute Myeloid Leukemia (AML): Correlation between Mutation Clearance and Clinical Response
Abstract Code: P207
Session Title: Acute Myeloid Leukemia – Clinical 2
Date and Time: Friday, June 23, 17:15 – 18:45 CEST (1:15 p.m. – 2:45 p.m. EDT)

About Pracinostat
Pracinostat is a potential best-in-class, oral histone deacetylase (HDAC) inhibitor that is in late stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for Pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for Pracinostat in AML and other potential indications. The deal provides the complementary resources from both organizations to rapidly advance Pracinostat into Phase III clinical development and expand into additional areas of clinical development, including high-risk myelodysplastic syndrome (MDS). Pracinostat is an investigational agent and is not approved for use in the U.S.

About AML
Acute myeloid leukemia (also known as acute myelogenous leukemia) is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 21,380 new cases of AML per year in the U.S., with an average age of about 67 years. Front line treatment consists primarily of induction chemotherapy, while the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend hypomethylating agents azacitidine or decitabine as low intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.

Foundation Medicine and Its Collaborators to Present New Data at ASCO 2017 Supporting the Integration of Comprehensive Genomic Profiling (CGP) in Personalized Clinical Care in Oncology

On May 18, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported that data from its suite of comprehensive genomic profiling (CGP) assays, including FoundationOne, FoundationACT liquid biopsy, FoundationOne Heme, and FoundationFocus CDxBRCA will be presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 2-6, 2017 in Chicago (Press release, Foundation Medicine, MAY 18, 2017, View Source [SID1234519213]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The company and its collaborators will present a total of 33 studies at the meeting, including two oral presentations, eight poster discussions and twenty-three posters, ranging across 15 different tumor types. Data demonstrate the impact of tissue- and blood-based CGP on guiding targeted therapy, immunotherapy, or clinical trial decisions in advanced cancers. In addition, the clinical value of CGP as evidenced through real world evidence and outcomes research (HEOR) studies, as well as data highlighting the ability of CGP to accelerate clinical trial enrollment will be presented.

"Together these studies highlight the importance of our CGP approach in advancing precision medicine in cancer care and build upon the growing body of evidence supporting its use in clinical practice," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "Previous findings from Foundation Medicine have shown that measuring tumor mutational burden (TMB) with FoundationOne can predict responses to FDA-approved anti-PD-1/anti-PD-L1 immunotherapies across multiple tumor types. New results will be presented at this year’s ASCO (Free ASCO Whitepaper) which help describe the landscape of TMB in triple-negative breast cancer, ovarian cancer, metastatic melanoma, biliary tract cancer and cancer of unknown primary, pointing to potentially new subsets of patients who may benefit from this therapeutic strategy. We believe these data will be critical to advancing the field of immunotherapy, and will be particularly insightful for clinicians, as well as biopharma companies seeking to advance immunotherapeutic agents. In addition, we’ll present exciting new data demonstrating the impact of our decision support tools on accelerating clinical trial enrollment – – helping to address an important need in cancer care."

New results include an oral presentation titled "Comprehensive genomic profiling with loss of heterozygosity to identify therapeutically relevant subsets of ovarian cancer," which shows that CGP can reveal molecular, rather than histologic, patient subsets who may benefit from poly (ADP-ribose) polymerase (PARP) inhibitor targeted therapy or immunotherapy. These results also provide support for insurance coverage and further integration of CGP into clinical trials in ovarian cancer.

Further supporting the integration of CGP at diagnosis, results from health economic and outcomes studies will be presented, demonstrating that early integration of CGP into a patient’s clinical and diagnostic work-up leads to improved patient outcomes associated with reasonable incremental costs to the payer that are largely driven by increased survival time on treatment. One poster titled "Estimated Cost of Anti-Cancer Therapy Directed by CGP in a Single-Center Study" discusses estimated anti-cancer drug costs and the associated cost impact of overall survival (OS) for matched vs. unmatched therapy in patients enrolled in a previously reported clinical trial using FoundationOne to guide therapeutic decisions.

In addition, important new studies will be presented on the ability of FoundationACT liquid biopsy assay to identify ESR1 and PIK3CA mutations in metastatic breast cancer, acquired resistance mutations in non-small cell lung cancer and BRCA1/2 reversion mutations in prostate cancer, all of which could help guide treatment decisions for these indications.

Other studies demonstrate the ability of CGP to accelerate clinical trial enrollment. Results from "Accelerating clinical trial enrollment with comprehensive genomic profiling (CGP) and ‘Just-in-Time’ clinical trial sites: An index case of a paradigm shift", reveal a new approach for matching patients to clinical trials that focus on rare genomic findings. Combined with a computational matching infrastructure, this approach could accelerate drug development and improve access to novel targeted therapies.

Following is a list of selected abstracts, including those referenced above.

Visit View Source for a complete list of abstracts and to stay connected with Foundation Medicine during the ASCO (Free ASCO Whitepaper) meeting.

Immunotherapy/TMB Data

Oral Presentation: Abstract 5512 – Comprehensive genomic profiling (CGP) with loss of heterozygosity (LOH) to identify therapeutically relevant subsets of ovarian cancer (OC), June 5, E450ab, 8:48am – 9:00am
Abstract 9536 – Landscape of genomic alterations (GA) and tumor mutational burden (TMB) in different metastatic melanoma (MM) subtypes, June 3, Hall A, 1:15pm – 4:45pm
Abstract 4086 – Tumor mutational burden (TMB) and co-existing actionable mutations in biliary tract cancers (BTC), June 3, Hall A, 8:00am – 11:30am
Abstract 3039 – Mutational burden of tumors with primary site unknown, June 5, Hall A, 8:00 am – 11:30am
Abstract 9072 – BRAF fusions in clinically advanced non-small cell lung cancer: An emerging target for anti-BRAF therapies, June 3, Hall A, 8:00am – 11:30am
Targeted Therapy Data

Oral Presentation: Abstract 11001 – Impact of next-generation sequencing (NGS) on diagnostic and therapeutic options in soft-tissue and bone sarcoma, June 2, S100bc, 3:12pm – 3:24pm
Abstract 3583 – Targeted therapy for HER2 driven colorectal cancer, June 3, Hall A, 8:00am – 11:30am
Health Economic Data

Abstract 6599 – Comprehensive genomic profiling (CGP) versus conventional molecular diagnostic testing of patients with advanced non-small cell lung cancer (NSCLC): Overall survival (OS) and cost in US health plan population, June 5, Hall A, 1:15pm – 4:45pm
Abstract 6605 – Estimated cost of anti-cancer therapy directed by comprehensive genomic profiling (CGP) in a single-center study, June 5, Hall A, 1:15pm – 4:45pm
Liquid Biopsy Data

Abstract 1016 – Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with metastatic breast cancer (mBC), June 4, Hall B1, 4:45pm – 6:00pm
Abstract 9025 – Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced non-small cell lung cancer (NSCLC), June 3, Hall A, 8:00am – 11:30am
Abstract 5024 – BRCA1/2 reversion mutations in prostate cancer identified from clinical tissue and liquid biopsy samples, June 5, Hall A, 1:15pm – 4:45pm
Abstract 4128 – Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with pancreatic ductal adenocarcinoma (PDA), June 3, Hall A, 8:00am – 11:30am
Clinical Trial and Partnerships Data

Abstract 6539 – Accelerating clinical trial enrollment with comprehensive genomic profiling (CGP) and just-in-time clinical trial sites: An index case of a paradigm shift, June 5, Hall A, 1:15pm – 4:45pm
Abstract 2512 – Personalized, molecularly matched combination therapies for treatment-naïve, lethal malignancies: The I-PREDICT study, June 5, Arie Crown Theater, 11:30am – 12:45pm

Epizyme Announces Path Toward Tazemetostat Registration in Epithelioid Sarcoma and Reports New Clinical Data to be Presented at ASCO

On May 18, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported positive interim data on its first-in-class EZH2 inhibitor, tazemetostat, from the epithelioid sarcoma cohort of its ongoing Phase 2 study in adult patients with molecularly defined solid tumors (Press release, Epizyme, MAY 18, 2017, View Source [SID1234519211]). In addition, the Company announced that it recently conducted a positive meeting with the U.S. Food and Drug Administration (FDA) to discuss the registration strategy for tazemetostat for the treatment of epithelioid sarcoma. Based on discussions with the FDA, the Company has identified a path to submission for accelerated approval of tazemetostat based on the 60-patient cohort from its Phase 2 study, and will target a New Drug Application (NDA) submission in 2018.

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An interim assessment of the epithelioid sarcoma cohort of patients (n=31), as of May 1, 2017, shows that treatment with tazemetostat resulted in a 32 percent disease control rate and a 13 percent overall response rate, with a median duration of response of seven months and ongoing. In addition, tazemetostat continues to demonstrate a favorable safety profile.

"Epithelioid sarcoma is a difficult cancer for sarcoma oncologists like me to treat due to there being few available therapeutic options, which are associated with limited benefit and challenging side effects for patients," said Mrinal M. Gounder, M.D., attending physician at Memorial Sloan Kettering Cancer Center and lead investigator in the Phase 2 clinical trial. "INI1 loss is a defining feature of epithelioid sarcoma and the mechanism of tazemetostat makes this a compelling agent. These data show encouraging activity of tazemetostat as characterized by objective responses, duration of responses and prolonged disease stabilization, and I look forward to its continued development."

"Bringing tazemetostat to patients is our number one priority," said Robert Bazemore, president and chief executive officer of Epizyme. "We stand today with a line of sight to an expedited pathway of bringing tazemetostat to patients with this rare and devastating form of cancer. I am very proud of the hard work and dedication of the entire Epizyme team in advancing tazemetostat this far, so that we may provide a new treatment option to patients who are in desperate need of effective and tolerable medicines."

Phase 2 Study in Molecularly Defined Solid Tumors
Epizyme’s Phase 2 study is evaluating the efficacy and safety of 800mg of tazemetostat orally administered twice-daily in adult patients with certain molecularly defined solid tumors, stratified into five different cohorts based on tumor type, including: epithelioid sarcoma, synovial sarcoma, malignant rhabdoid tumor, renal medullary carcinoma and other INI1-negative tumors.

Epizyme will present interim efficacy data from the epithelioid sarcoma and synovial sarcoma cohorts and safety data from all cohorts at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The remaining three arms of the study have not yet reached futility assessment by the Independent Data Monitoring Committee. Epizyme anticipates providing updates from those cohorts later in 2017.

Epithelioid Sarcoma Efficacy Data
The epithelioid sarcoma cohort in Epizyme’s Phase 2 study represents the largest prospective study of epithelioid sarcoma with any approved or investigational treatment to date. Epithelioid sarcoma is an ultra-rare and aggressive soft tissue sarcoma, characterized by a loss of the INI1 protein. It is most commonly diagnosed in young adults (20-40 years old) and is often fatal. There is no established standard-of-care for treating these patients, who are typically resistant to chemotherapy.

The cohort was initially designed to enroll 30 patients, and was expanded to enroll an additional 30 patients in December 2016 based on encouraging early activity. The cohort has enrolled 49 front-line and relapsed or refractory epithelioid sarcoma patients out of a projected total of 60 patients. Interim data to be presented are from 31 patients in the initial study group, as of the data cutoff on May 1, 2017.

In these patients, tazemetostat treatment resulted in a 32 percent disease control rate (DCR), the primary endpoint. DCR is comprised of confirmed objective responses by RECIST 1.1 for any duration or disease stabilization of 32 weeks or more. Thus far, four patients (13%) have achieved confirmed objective responses (all partial), and the time to response ranged from two months to six months. The median duration of response is seven months and ongoing. Prolonged disease stabilization of 32 weeks or more has been observed in six patients (19%), including two patients having stable disease for more than 15 months. These Phase 2 data complement the Company’s experience from its Phase 1 study, in which two of three patients with epithelioid sarcoma remain on tazemetostat with stable disease out over two years.

A median progression-free survival (PFS) of 5.7 months has been observed, and initial assessment of overall survival for those patients in the DCR group compared to the non-DCR group showed distinct separation in survival curves, favoring the DCR group. The data from this cohort are still maturing, and an initial assessment suggests the potential for prolonged clinical benefit with tazemetostat treatment.

These interim data will be presented at ASCO (Free ASCO Whitepaper) by Dr. Gounder in a poster titled "Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with INI1 negative epithelioid sarcoma (NCT02601950)" on June 4 (Abstract No.: 11058, Poster Board No.: 381).

Tazemetostat Safety Profile
Tazemetostat has demonstrated a favorable safety profile in the Phase 2 study, particularly when considering the adverse effects associated with currently utilized chemotherapeutic regimens and other STS therapies. Safety data from patients in all study cohorts (n=121) are consistent with the overall safety profile observed in a nearly 400 patient-safety database from tazemetostat clinical trials to date, showing favorable tolerability without significant safety events. There were no discontinuations due to adverse events in any of the study cohorts. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2, with only 12 percent of patients experiencing grade 3 or higher treatment-related TEAEs. Reported TEAEs regardless of attribution with an incidence of 10 percent or greater were fatigue (34%), dyspnea and nausea (27% each), cough (22%), decreased appetite (20%), vomiting (19%), constipation (18%), anemia (17%), diarrhea (16%), back pain and headache (12% each), pleural effusion (11%) and death and peripheral edema (10% each). All deaths that occurred during the study were attributed to the patients’ underlying disease and not to treatment with tazemetostat.

There were no clinically relevant differences in the safety profile for either the epithelioid sarcoma or the synovial sarcoma cohorts compared to that of the entire study.

Synovial Sarcoma Efficacy Data
The cohort of patients with synovial sarcoma (n=33) in the Phase 2 study completed enrollment in November 2016. Data show tazemetostat treatment resulted in stable disease as the best response in 10 patients (30%) with five patients (15%) meeting the primary endpoint of disease stabilization for 16 weeks or longer. The level of activity was determined to be insufficient to advance tazemetostat as a monotherapy for this tumor type.

These data will be presented in a poster by Patrick Schöffski, M.D., Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospitals Leuven, KU Leuven, Belgium, titled "Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with synovial sarcoma (NCT02601950)" on June 4 (Abstract No.: 11057, Poster Board No.: 380).

Conference Call Information
Epizyme will host a conference call and audio webcast today at 8:30 a.m. Eastern Time. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 12186629. The webcast, and accompanying slides for the call, can be accessed under "Events and Presentations" in the Investor Relations section of the company’s website at www.epizyme.com.

About Epithelioid Sarcoma
Epithelioid sarcoma is an ultra-rare soft tissue sarcoma characterized by a loss of function of the protein INI1. Patients are most commonly diagnosed as young adults, between 20 and 40 years of age. Median overall survival from initial diagnosis is 30 months. Epithelioid sarcoma becomes more aggressive after recurrence or metastases, with a typical survival of eight to 12 months for patients with metastatic disease. There is no approved treatment indicated specifically for epithelioid sarcoma, and there is no established standard of care.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma; and mesothelioma; as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for both relapsed/refractory follicular lymphoma with or without an EZH2 activating mutation and DLBCL with EZH2 activating mutations, as well as Orphan Drug designation for malignant rhabdoid tumors.