On June 3, 2021 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported positive results from the pivotal study "JUPITER-02", a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) (Press release, Coherus Biosciences, JUN 3, 2021, View Source [SID1234583499]). The interim analysis met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression free survival (PFS) compared to chemotherapy alone (assessed by a blinded independent review committee, or BIRC, per RECIST v1.1). JUPITER-02 also met secondary endpoints of PFS assessed by the investigator and objective response rate (ORR) assessed by BIRC. There was also a longer duration of response (DoR), a higher disease control rate (DCR) and higher one- and two-year survival rates for the toripalimab arm. The safety profile of toripalimab was consistent with that observed in previously reported toripalimab clinical trials.

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The results are summarized in a late-breaking abstract that will be presented during a plenary session at the 2021 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) on Sunday, June 6, 2021 from 1–4 pm Eastern Daylight Time. The abstract (LBA2) is now available on the ASCO (Free ASCO Whitepaper) website.

"Nasopharyngeal carcinoma is an aggressive tumor—especially for patients with advanced NPC. For first line treatment, platinum-based chemotherapy remains the current standard of care, yet mPFS is only about 7 months. We are encouraged by the JUPITER-02 results showing the addition of toripalimab to chemotherapy as first-line treatment provided superior PFS and ORR and longer DoR than chemotherapy alone, and with a safety and tolerability profile consistent with the PD-1 antibody class of drugs," said Dr. Ruihua Xu, President and Professor, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou. "I believe that these results support the use of toripalimab with chemotherapy as the new standard of care for first-line treatment of patients with recurrent/metastatic NPC."

More than 30 toripalimab abstracts were accepted for ASCO (Free ASCO Whitepaper) 2021, including two selected for oral presentations (LBA2 and #9512), describing the antitumor activities observed from various cancers of the nasopharynx, skin, lung, esophagus, stomach, liver, biliary duct, head and neck, and pancreas. Importantly, ten of the abstracts demonstrated toripalimab’s potential in perioperative, adjuvant, or neoadjuvant treatment settings.

"Given the outstanding results, JUPITER-02 is the first study to show a major therapeutic advance for first-line treatment of advanced NPC since the chemotherapy combination of gemcitabine and cisplatin was established as standard of care, which is why I believe this study was selected for presentation at the plenary session at ASCO (Free ASCO Whitepaper) 2021. We will work to expedite commercialization of toripalimab for this patient population in China, the United States, and other countries to make this exciting new treatment option broadly available to all patients with NPC," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "In addition to the JUPITER-02 trial, results of multiple other studies of toripalimab will be presented during the ASCO (Free ASCO Whitepaper) annual meeting, which support the current development strategy, such as perioperative immunotherapy in patients with multiple solid tumors, including mucosal melanoma, esophageal cancer, gastric cancer, liver cancer and non-small cell lung cancer, as well as the exploration of toripalimab for treatment of ICC, for which no checkpoint inhibitors have been approved for use."

"ASCO 2021 is a pivotal moment for Coherus as it marks the U.S. medical meeting debut of the immuno-oncology franchise we are building to deliver life-changing medicines addressing both rare and highly prevalent cancers," said Denny Lanfear, CEO of Coherus. "The strong late-breaking data in advanced NPC add to the favorable efficacy and safety profile that is emerging for toripalimab in the broad development program with more than 15 pivotal clinical trials. Alongside Junshi Biosciences, we look forward to presenting clinical data from these studies and to working together to register toripalimab in the United States and Canada as a potential new therapeutic option across a broad range of tumor types, starting with NPC."

About JUPITER-02 Results

JUPITER-02, conducted in mainland China, Taiwan and Singapore, is the largest Phase 3 clinical study to evaluate a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. Two hundred eighty-nine patients with advanced NPC who had received no prior chemotherapy for recurrent/metastatic disease were randomized 1:1 to receive toripalimab 240 mg or placebo in combination with gemcitabine 1000 mg/m2 (d1, 8) and cisplatin 80 mg/m2 (d1), Q3W followed by toripalimab or placebo monotherapy until disease progression, intolerable toxicity or completion of two years of treatment. Progression-free survival and response were assessed by the BIRC and by the investigator per RECIST v1.1. There was one pre-specified interim analysis of PFS at 130 (65%) PFS events with a planned final analysis at 200 PFS events.

By May 30, 2020, the date of the interim analysis data cut, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. The ASCO (Free ASCO Whitepaper) presentation also includes an updated overall survival (OS) analysis with a data cut-off of February 18, 2021.

A summary of the results is as follows:

A significant improvement in PFS (assessed by BIRC) was observed in the toripalimab plus chemotherapy arm compared to the chemotherapy alone arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), median PFS of 11.7 vs. 8.0 months;
The 1-year PFS rates were 49% and 28%, respectively, for the toripalimab arm compared to the placebo arm;
An improvement in PFS was observed across relevant subgroups including patients with high PD-L1 expression (TC or IC ≥ 1%; mPFS 11.4 vs. 8.2 month, HR = 0.59 [95% CI: 0.388 – 0.893]) or low PD-L1 expression (TC and IC<1%; mPFS 11.0 vs. 6.0 months, HR=0.35 [95% CI: 0.153 – 0.808]);
The ORR was 77.4% vs. 66.4% (P = 0.034); the median DoR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]), P = 0.001);
The first interim analysis of overall survival was not mature at the interim analysis of PFS. In the updated OS analysis conducted February 18, 2021, although median OS was not yet mature in either arm, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.60 [95% CI: 0.364-0.997], nominal P = 0.046);
The incidence of grade ≥3 treatment emergent adverse events (TEAEs) (89.0% vs 89.5%), grade ≥3 treatment related adverse events (TRAE) (80.8% vs 83.2%), AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%), and fatal AEs (2.7% vs 2.8%) was similar between both arms. Immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab group.
A pre-specified second interim OS analysis will be performed at the same time as the final PFS analysis.

About toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China and the United States. Pivotal clinical trials are ongoing or completed evaluating the safety and efficacy of toripalimab for a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). On December 17, 2018, toripalimab was granted a conditional approval from the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, the supplemental NDA for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA. In the same month, the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April, NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

In the United States, a rolling submission of the first toripalimab Biologics License Application (BLA) is underway for the treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC). The U.S. Food and Drug Administration (FDA) has granted toripalimab Breakthrough Therapy Designation for this indication. There are currently no PD-1 blocking antibodies indicated for use in NPC in the United States. Additionally, FDA has granted Fast Track status for the development of toripalimab for the treatment of mucosal melanoma and orphan drug designation for NPC, mucosal melanoma and soft tissue sarcoma. Earlier in 2021 Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple rare cancers and highly prevalent cancers.

On June 3, 2021 AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported the first presentation of data from the Phase 3 OlympiA trial, in which LYNPARZA demonstrated a statistically significant improvement in its primary endpoint of invasive disease-free survival (iDFS) versus placebo in the adjuvant treatment of patients with germline BRCA1/2 mutations and high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer following definitive local treatment and neoadjuvant or adjuvant chemotherapy (Press release, Merck & Co, JUN 3, 2021, View Source [SID1234583498]). Results will be presented during the Plenary Session at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6 (Abstract LBA#1). Results were also published today in the New England Journal of Medicine.

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An estimated 2.3 million people were diagnosed with breast cancer worldwide in 2020, and germline BRCA mutations are found in approximately 5% of patients with breast cancer.

OlympiA is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. In the overall trial population of 1,836 patients, results showed LYNPARZA (n=921) reduced the risk of invasive breast cancer recurrences, second cancers or death by 42% (HR=0.58 [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo (n=915) based on a pre-specified event-driven interim analysis with a median follow-up of 2.5 years. At three years following trial initiation, 85.9% of patients treated with LYNPARZA were alive and free of invasive breast cancer and second cancers versus 77.1% of patients treated with placebo (difference: 8.8% [95% CI, 4.5-13.0]).

Results also showed an improvement in the key secondary endpoint of distant disease-free survival (DDFS) in the overall trial population. LYNPARZA reduced the risk of distant disease recurrence or death by 43% (HR=0.57 [99.5% CI, 0.39-0.83]; p<0.0001). At the time of data cut-off, overall survival (OS) data, while directionally encouraging, did not reach statistical significance and were not mature. The trial will continue to assess OS as a secondary endpoint.

The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse events (AEs) (≥20%) were nausea (57%), fatigue (40%), anemia (23%) and vomiting (23%). Grade ≥3 AEs were anemia (9%), neutropenia (5%), leukopenia (3%), fatigue (2%) and nausea (1%). Approximately 10% of patients treated with LYNPARZA discontinued treatment due to AEs.

Andrew Tutt, chair of the OlympiA trial steering committee and professor of oncology, The Institute of Cancer Research, London, and Kings College London, said, "We are thrilled that our global academic and industry partnership in OlympiA has been able to help identify a possible new treatment option for patients with early-stage breast cancer and who have inherited mutations in their BRCA1 or BRCA2 genes. Patients with early-stage breast cancer who have inherited BRCA mutations are typically diagnosed at a younger age compared to those without such a mutation. Olaparib has the potential to be used as a follow-on to all the standard initial breast cancer treatments to reduce the rate of life-threatening recurrence and cancer spread for many patients identified through genetic testing to have mutations in these genes."

Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, "By providing a treatment which significantly reduces the risk of breast cancer returning in these high-risk patients, we hope LYNPARZA will set a new benchmark. We are working with regulatory authorities to bring LYNPARZA to these patients as quickly as possible."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "Results of the OlympiA trial represent a potential step forward for patients with high-risk early breast cancer. These new data support the importance of testing at diagnosis for BRCA1/2 mutations, which are actionable biomarkers that can help identify patients with early breast cancer who may be eligible for adjuvant treatment with LYNPARZA. Testing for BRCA mutations, in addition to hormone receptor status and the expression of the HER2 protein, will allow clinicians to better inform potential treatment plans for their patients."

In February 2021, the Independent Data Monitoring Committee (IDMC) recommended for the OlympiA trial to move to early primary analysis and reporting. Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of iDFS.

Summary of OlympiA Results

LYNPARZA
(n=921)

Placebo
(n=915)

iDFS (primary endpoint)

HR (99.5% CI)

0.58 (0.41, 0.82)

p-value

p<0.0001

Events

106

178

iDFS ratesiii

One year

93.3%

88.4%

Two years

89.2%

81.5%

Three years

85.9%

77.1%

DDFS (secondary endpoint)

HR (99.5% CI)

0.57 (0.39, 0.83)

p-value

p<0.0001

Events

89

152

DDFS ratesiii

One year

94.3%

90.2%

Two years

90.0%

83.9%

Three years

87.5%

80.4%

OS at interim (secondary endpoint)ii

HR (99% CI)

0.68 (0.44, 1.05)

p-value

p=0.024

Events

59

86

OS ratesiii

One year

98.1%

96.9%

Two years

94.8%

92.3%

Three years

92.0%

88.3%

i
The data cut-off date for the interim analysis was March 27, 2020.

ii
Statistical significance was not reached based on the interim analysis plan for alpha conservation for future survival analyses.

iii
The study was not designed to assess a statistical difference between treatment groups at these timepoints.

OlympiA is a global, collaborative, Phase 3 trial coordinated by the Breast International Group (BIG) worldwide, in partnership with NRG Oncology, the U.S. National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and Merck. The trial is sponsored by NRG Oncology in the U.S. and by AstraZeneca outside the U.S.

LYNPARZA is approved in the U.S., Japan and a number of other countries for germline BRCA-mutated, HER2-negative metastatic breast cancer previously treated with chemotherapy and, if hormone receptor-positive, endocrine therapy if appropriate. In the EU, this includes locally advanced breast cancer.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

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 0.8% of patients exposed to LYNPARZA monotherapy, 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.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

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%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

DRUG INTERACTIONS

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

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using 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 in the United States

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.

HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. 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).

About Breast Cancer

Breast cancer is the most common cancer among women worldwide, and an estimated 70% of all breast cancer cases are diagnosed at an early stage. Breast cancer is one of the most biologically diverse tumor types with various factors underlying its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted the scientific understanding of the disease and the treatment of patients who develop the disease.

About BRCA Mutations

BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About OlympiA

OlympiA is a Phase 3, double-blind, parallel-group, placebo-controlled, multicenter trial evaluating the efficacy and safety of LYNPARZA versus placebo as adjuvant treatment in patients with gBRCAm high-risk HER2-negative early breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomized to LYNPARZA (300 mg twice daily) or placebo. The primary endpoint of the trial is iDFS, which is defined as time from randomization to date of first loco-regional or distant recurrence or new cancer or death from any cause. Key secondary endpoints include OS and DDFS, which is defined as time from randomization until documented evidence of first distant recurrence of breast cancer or death without distant recurrence.

About BIG

The Breast International Group (BIG) is an international not-for-profit organization for academic breast cancer research groups from around the world, based in Brussels, Belgium.

Founded by leading European opinion leaders in 1999, the organization aims to address fragmentation in breast cancer research and now represents a network of over 50 like-minded research groups affiliated with specialized hospitals, research centers and leading experts across approximately 70 countries on six continents.

BIG’s research is supported in part by its philanthropy unit, known as BIG against breast cancer, which is used to interact with the general public and donors, and to raise funds for BIG’s purely academic breast cancer trials and research programs.

About FSTRF

Frontier Science & Technology Research Foundation (FSTRF) is a non-profit, research organization which supports research networks, pharmaceutical companies and investigators to conduct scientifically meaningful high-quality clinical trials. The OlympiA trial involved research staff in the U.S. and in the Affiliate office in Scotland.

FSTRF works with scientists and technicians in more than 800 laboratories, universities and medical centers around the world to provide a comprehensive range of research services throughout the clinical trial process including design, analysis and reporting.

Through its work, FSTRF aims to advance the application of statistical science and practice and data management techniques in science, healthcare and education.

About NRG Oncology

NRG Oncology is a network group funded by the U.S. National Cancer Institute (NCI), a part of the National Institutes of Health.

NRG Oncology brings together the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG), with the mission to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research. NRG Oncology sponsored OlympiA in the U.S. and collaborated with the other adult cancer clinical trials research groups funded by the NCI, Alliance, ECOG/ACRIN and the Southwest Oncology Group. The NCI and AstraZeneca are collaborating under a Cooperative Research and Development Agreement between the parties.

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.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

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.

On June 3, 2021 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies and infectious disease vaccines based on the Company’s proprietary Versamune T-cell activating technology, reported the protocol amendment to expand its Phase 2 VERSATILE-002 study to include patients, in an additional arm, who have failed prior checkpoint inhibitor (CPI) therapy (CPI refractory patients) (Press release, PDS Biotechnology, JUN 3, 2021, View Source [SID1234583497]). The VERSATILE-002 study is designed to evaluate PDS0101 in combination with KEYTRUDA (pembrolizumab) in the treatment of advanced human papillomavirus (HPV)-associated head and neck cancer and is currently being run at approximately 20 clinical sites in the US.

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VERSATILE-002 was initially opened to checkpoint inhibitor naive HPV16-associated head and neck cancer patients in first line treatment of recurrent or metastatic cancer. The trial is actively recruiting patients who have the option to receive the two immunotherapies rather than chemotherapy as their first line of treatment for recurrent disease. The additional study arm will evaluate the objective response to the combination among approximately 40 patients with advanced head and neck cancer who have failed multiple treatments, including checkpoint inhibitor therapy. Objective response is measured by radiographic tumor responses according to RECIST 1.1. In the expansion arm, the first 21 patients will be evaluated for safety and objective response before the arm progresses to full enrollment.

The inclusion of CPI refractory patients in VERSATILE-002 follows the publication of an abstract and subsequent presentation of interim data in another Phase 2 trial (NCT04287868) being led by the National Cancer Institute (NCI) evaluating the combination of PDS0101 (Versamune-HPV16) in combination with two investigational immunotherapies. That trial recently reported clinical responses with objective responses (tumor reduction of 30% or more) in 63% (5/8) of HPV16-positive cancer patients who had failed chemotherapy, radiation, and checkpoint inhibitor therapy.

"There is an enormous unmet medical need in advanced head and neck cancer patients who have failed multiple therapies, including chemotherapy, radiation and checkpoint inhibitor therapy. We believe the combination of PDS0101 and KEYTRUDA has the potential to significantly improve clinical outcomes for these patients who have limited treatment options," commented Dr. Lauren Wood, Chief Medical Officer of PDS Biotech.

Dr. Jared Weiss, Associate Professor of Medicine, Division of Oncology, University of North Carolina at Chapel Hill School of Medicine and Lineberger Comprehensive Cancer Center, is serving as the Principal Investigator of this Phase 2 clinical trial in advanced HPV16-associated head and neck cancer. For patients interested in learnings more about this clinical study, please visit the website: View Source

On June 3, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that the first patient has been dosed in the Company’s Phase 1b study of VIP152 in MYC-driven relapsed or refractory (R/R) aggressive lymphomas and advanced solid tumors (Press release, Vincerx Pharma, JUN 3, 2021, View Source [SID1234583496]).

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"Vincerx has achieved a significant milestone with the first dosing of a patient in a Vincerx-sponsored clinical trial," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "This trial builds upon the encouraging signals of monotherapy activity observed in the dose-escalation study and exploratory cohort in double-hit lymphoma, which includes clinically significant monotherapy activity in patients with advanced malignancies and a favorable safety profile. We believe our comprehensive clinical strategy, which explores the potential of potent and specific PTEFb/CDK9 inhibition with VIP152 in MYC-driven indications, positions us to pursue multiple registration paths. We look forward to the continued expansion of our strategic clinical programs with the initiation of our Phase 1 dose escalation study in CLL relapsed/refractory to venetoclax and BTK inhibitors in the second half of this year."

The ongoing Phase 1b expansion, first-in-human (FIH) study is in patients with advanced cancer and consists of two expansion arms. Arm 1 will enroll up to 30 patients with relapsed/refractory aggressive lymphoma, including DLBCL, transformed follicular lymphoma, and blastoid mantle cell lymphoma. Arm 2 will enroll up to 40 patients with advanced solid tumors, including patients with ovarian cancer, triple negative breast cancer, castration-resistant neuroendocrine prostate cancer, and any other solid tumor with MYC aberration. All patients must have confirmed MYC overexpression or translocation.

Previously, early signs of clinical activity at higher dose levels were observed with durable disease control in individual patients with pancreatic cancer and salivary gland cancer (~10 and ~17 months of treatment, respectively). Of the 31 subjects dosed, a patient with double-hit lymphoma (DHL) from the 30-mg cohort achieved a complete metabolic response (CMR) followed by the enrollment of an additional 6 DHL patients in an exploratory cohort with a CMR observed in 29% (2 of 7) patients. Due to the COVID pandemic, the patients with CMR withdrew consent after 3.7 and 2.3 years, respectively, of treatment. Both patients were in CMR at study exit.

On June 3, 2021 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, reported that Emil D. Kakkis, M.D., Ph.D., the company’s Chief Executive Officer and President, will present at the Goldman Sachs 42ND Annual Healthcare Conference on Thursday, June 10, 2021 at 3:00 PM ET (Press release, Ultragenyx Pharmaceutical, JUN 3, 2021, View Source [SID1234583495]).

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The live and archived webcast of the presentation will be accessible from the company’s website at View Source The replay of the webcast will be available for 90 days.