On March 4, 2015 Eisai Co., and Merck reported on a clinical trial collaboration to evaluate the safety, tolerability and efficacy of Merck’s anti-PD-1 therapy, pembrolizumab (marketed in the U.S. under the brand name KEYTRUDA), in combination with Eisai oncology compounds
lenvatinib mesylate (a multi-targeting RTK inhibitor marketed in the U.S. under the brand name LENVIMA, “lenvatinib”) and eribulin mesylate (a microtubule dynamics inhibitor marketed in
nearly 60 countries including Japan, the U.S., and Europe under the brand name HALAVEN, “eribulin”) in multiple clinical trials (Press release, Eisai, MAR 4, 2015, View Source [SID:1234502182]).

The planned studies include a multicenter, open-label Phase 1b/2 study of lenvatinib plus pembrolizumab in select solid tumors and an open-label, single-arm, multicenter Phase1b/2 study to evaluate the efficacy and safety of eribulin in combination with pembrolizumab in metastatic triple-negative breast cancer. Eisai and Merck will establish a Joint Development Committee to oversee clinical development activities. The studies are expected to begin in
the second half of 2015. Financial terms of the agreement were not disclosed.

“This collaboration could be a major step in the direction of developing combination regimens in different types of cancer, potentially maximizing the value of eribulin and lenvatinib,” said
Kenichi Nomoto, PhD, president, oncology product creation unit, Eisai Product Creation Systems. “Together, Eisai and Merck seek to explore combination regimens that have the potential to create synergistic effects between lenvatinib and pembrolizumab as well as between eribulin and pembrolizumab. Our hope is that we will bring treatments to market that make a difference in the lives of people battling cancer.”

“Cancer is a complex disease that often requires different approaches to help patients achieve the best possible outcome,” said Dr. Eric Rubin, therapeutic area head, oncology early-stage development, Merck Research Laboratories. “The collaboration with Eisai exemplifies Merck’s focus on advancing breakthrough science in immuno-oncology. We look forward to evaluating pembrolizumab in combination with eribulin and also with lenvatinib in different tumor types.”

The combinations of lenvatinib and pembrolizumab, and eribulin and pembrolizumab, are investigational. The efficacy and safety of these combinations have not been established.

On March 4, 2015 Bristol-Myers Squibb reported that the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection, for intravenous use, for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Press release, Bristol-Myers Squibb, MAR 4, 2015, View Source [SID:1234502174]). Opdivo is the first and only PD-1 (programmed death receptor-1) therapy to demonstrate overall survival in previously treated metastatic squamous NSCLC. Opdivo demonstrated significantly superior overall survival (OS) vs. docetaxel, with a 41% reduction in the risk of death (hazard ratio: 0.59 [95% CI: 0.44, 0.79; p=0.00025]), in a prespecified interim analysis of a Phase III clinical trial. The median OS was 9.2 months in the Opdivo arm (95% CI: 7.3, 13.3) and 6 months in the docetaxel arm (95% CI: 5.1, 7.3).

“Bristol-Myers Squibb is committed to patients with lung cancer, and we are pleased to offer Opdivo as the first immuno-oncology therapy for patients who have previously treated metastatic squamous NSCLC,” said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. “Because lung cancer is one of the most commonly diagnosed cancers in the United States, with high mortality, there is a significant need for treatments that extend survival. We’re thankful to the many patients and healthcare providers that partnered with us to develop a new treatment that has the potential to address that unmet need.”

This approval is the second for Opdivo in the United States within three months, and is based on the results of CheckMate -017 and CheckMate -063.

Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism, other adverse reactions; and embryofetal toxicity. Please see the Important Safety Information section below.

Proven Superior Survival vs. Standard of Care in a Phase III Clinical Trial

CheckMate -017 was a landmark Phase III, open-label, randomized, multinational, multicenter clinical trial that evaluated Opdivo (3 mg/kg intravenously over 60 minutes every two weeks) (n=135) vs. standard of care, docetaxel (75 mg/m2 intravenously administered every 3 weeks) (n=137), in patients with metastatic squamous NSCLC who had progressed during or after prior platinum doublet-based chemotherapy regimen. This trial included patients regardless of their PD-L1 (programmed death ligand-1) status. The primary endpoint of this trial was overall survival (OS).

In January, the trial was stopped based on an assessment conducted by the independent Data Monitoring Committee (DMC), which concluded that the study met its endpoint, demonstrating superior OS in patients receiving Opdivo compared to docetaxel. The prespecified interim analysis was conducted when 199 events (86% of the planned number of events for final analysis) were observed (86 in the Opdivo arm and 113 in the docetaxel arm).

Opdivo is the only FDA-approved monotherapy to demonstrate proven superior OS compared to standard of care in more than 15 years in previously treated metastatic squamous NSCLC. The median OS was 9.2 months in the Opdivo arm (95% CI: 7.3, 13.3) and 6 months in the docetaxel arm (95% CI: 5.1, 7.3). The hazard ratio was 0.59 (95% CI: 0.44, 0.79; p=0.00025). This hazard ratio translates to a 41% reduction in the risk of death with Opdivo compared to docetaxel.

“The FDA approval of Opdivo introduces an entirely new treatment modality that has demonstrated unprecedented results for the treatment of previously treated metastatic squamous NSCLC, with the potential to replace chemotherapy for these patients,” said Dr. Suresh Ramalingam, MD, Professor and Director of Medical Oncology, Winship Cancer Institute of Emory University. “This milestone brings to fruition the long-held hope that immuno-oncology medicines can be significantly effective in this difficult-to-treat population.”

About the CheckMate -063 Trial and the Safety Profile of Opdivo

The safety profile of Opdivo in squamous NSCLC was established in CheckMate -063, a Phase II single-arm, open-label, multinational, multicenter trial of Opdivo, administered as a single agent in patients with metastatic squamous NSCLC who have progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen (n=117). Patients received 3 mg/kg of Opdivo administered intravenously over 60 minutes every 2 weeks. This trial included patients regardless of their PD-L1 status. The most common adverse reactions (reported in ≥20% of patients) were fatigue (50%), dyspnea (38%), musculoskeletal pain (36%), decreased appetite (35%), cough (32%), nausea (29%), and constipation (24%). Serious adverse reactions occurred in 59% of patients receiving Opdivo. The most frequent serious adverse reactions reported in ≥2% of patients were dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation, pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain. Opdivo was discontinued due to adverse reactions in 27% of patients. Twenty-nine percent of patients receiving Opdivo had a drug delay for an adverse reaction.

With at least 10 months of minimum follow up for all patients, the confirmed objective response rate (ORR), the study’s primary endpoint, was 15% (17/117) (95% CI = 9, 22) of which all were partial responses. The median time to onset of response was 3.3 months (range: 1.7 to 8.8 months) after the start of Opdivo treatment. Seventy-six percent of Opdivo responders (13/17 patients) had ongoing responses with durability of response ranging from 1.9+ to 11.5+ months; 10 of these 17 (59%) patients had durable responses of 6 months or longer.

“The approval of Opdivo for the treatment of previously treated metastatic squamous non-small cell lung cancer is a major advancement in delivering extended survival for patients fighting this deadly disease,” said Andrea Ferris, President and Chairman, Lungevity Foundation. “We are very excited for an immuno-oncology therapy to enter the market and offer options and hope for many of our patients. I applaud the FDA and Bristol-Myers Squibb for their work in making this important and first of its kind treatment available to patients so quickly.”