LYNPARZA® (olaparib) Phase 3 SOLO3 Trial Demonstrated a 72% Objective Response Rate in Patients with Platinum-Sensitive Relapsed Germline BRCA-mutated Advanced Ovarian Cancer Compared to 51% of Patients Receiving Chemotherapy

AstraZeneca and Merck’s LYNPARZA Increased the Median Time Without Disease Progression or Death by 4.2 Months Versus Physician’s Choice of Chemotherapy Following Two or More Prior Lines of Chemotherapy

AstraZeneca and Merck’s LYNPARZA is the First and Only PARP Inhibitor to Demonstrate Efficacy Versus Chemotherapy in This Setting

KENILWORTH, NJ, USA I June 03, 2019 I AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States and Canada), today presented full results from the Phase 3 SOLO3 trial which evaluated LYNPARZA, compared to chemotherapy, for the treatment of platinum-sensitive relapsed patients with germline BRCA1/2-mutated (gBRCAm) advanced ovarian cancer, who have received two more prior lines of chemotherapy. The results were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

The results from the trial showed a statistically-significant and clinically-meaningful improvement in objective response rate (ORR) in the LYNPARZA arm compared to the chemotherapy arm (ORR; 72.2% for LYNPARZA vs 51.4% for chemotherapy; 95% CI: 1.40 to 4.58; p=0.002).

The key secondary endpoint of progression-free survival (PFS) was also significantly increased in the LYNPARZA arm (13.4 months) compared to the chemotherapy arm (9.2 months; PFS HR 0.62 [p=0.013]).

Summary of endpoints[i]
      LYNPARZA
(300 mg bd)
    Chemotherapy
ORR (primary endpoint)      
Number of patients     151     72
Number of patients with response (%)     109 (72.2%)     37 (51.4%)
Odds ratio (95% CI)     2.53 (1.40, 4.58)
p-value     0.002
PFS (key secondary endpoint)[ii]      
Number of patients     178     88
Number of patients with event (%)     110 (61.8%)     49 (55.7%)
Hazard ratio (95% CI)     0.62 (0.43, 0.91)
Median in months     13.4     9.2
p-value     0.013
       
iAssessed by blinded independent central review
iiAnalysis was done at 64.5% maturity
       

José Baselga, executive vice president, Oncology R&D, AstraZeneca, said, “This trial shows that LYNPARZA has the potential to provide a much-needed improvement and alternative over standard-of-care chemotherapy for certain patients with relapsed BRCA-mutated advanced ovarian cancer. This is the fourth positive Phase 2 or Phase 3 trial in advanced ovarian cancer for LYNPARZA across multiple lines of therapy. We look forward to discussing these results with regulatory authorities.”

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, “LYNPARZA is the first and only PARP inhibitor to demonstrate efficacy versus chemotherapy in relapsed BRCA-mutated advanced ovarian cancer following two or more prior lines of chemotherapy. The positive SOLO3 results reaffirm AstraZeneca and Merck’s ongoing commitment to explore potential treatment options beyond standard-of-care for BRCA-mutated patients with advanced stage disease.”

The safety and tolerability profile of LYNPARZA in SOLO3 was consistent with previous trials. The most common adverse events (AEs) ≥ 20% were nausea (64.6%), fatigue/asthenia (52.2%), anemia (51.1%), vomiting (38.2%), diarrhea (28.1%) and abdominal pain (21.3%). The most common ≥ Grade 3 AEs were anemia (21.3%), neutropenia (9.6%), fatigue/asthenia (4.5%) and thrombocytopenia (3.9%). AEs led to dose interruption in 48% percent of patients on LYNPARZA vs. 42% in the chemotherapy arm, while 7% of patients discontinued treatment vs. 20% in the chemotherapy arm.

LYNPARZA is currently approved in 64 countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is approved in the U.S. as first-line maintenance treatment in BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 38 countries, including the U.S., countries in the EU and Japan, for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy; in the EU this includes locally advanced breast cancer. Regulatory reviews are underway in other jurisdictions for both ovarian cancer and breast cancer.

About SOLO3
SOLO3 is a Phase 3 randomized, open-label, controlled, multi-center trial to evaluate the efficacy and safety of LYNPARZA tablets following two or more prior lines of chemotherapy. The trial randomized 266 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation. Eligible patients were randomized (2:1) to receive LYNPARZA 300mg tablets twice daily or physician’s choice single-agent chemotherapy (paclitaxel, topotecan, pegylated liposomal doxorubicin or gemcitabine). The primary endpoint was overall response rate (ORR) by blinded independent central review and key secondary endpoints included progression-free survival (PFS), time to second disease progression or death and overall survival.

About Ovarian Cancer
Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%. In 2018, there were over 295,000 new cases diagnosed and around 185,000 deaths. Over 70% of women with ovarian cancer have advanced disease at the time of diagnosis, with up to 80% at risk of recurrence after initial treatment. Effective treatments are needed in later lines of therapy as patients typically obtain limited benefit after two prior lines of chemotherapy.

About BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in 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 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.

INDICATIONS

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

First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients with gBRCAm advanced epithelial ovarian, fallopian tube or primary peritoneal cancer 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
In 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.

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

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 LYNPARZA, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib 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.

About Merck
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

SOURCE: Merck

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