The first overall survival data from the Phase 3 CheckMate -067 clinical trial

Bristol-Myers Squibb Company (NYSE:BMY) today announced the first overall survival (OS) data from the Phase 3 CheckMate -067 clinical trial. With a minimum follow-up of 28 months, the median OS had not yet been reached in either of the two Opdivo treatment groups and was 20 months for the Yervoy monotherapy group (95% CI: 17.1-24.6). Opdivo in combination with Yervoy and as a monotherapy reduced the risk of death 45% [hazard ratio (HR) 0.55; 95% CI: 0.42-0.72; P<0.0001] and 37% (HR 0.63; 95% CI: 0.48-0.81; P<0.0001), respectively, compared with Yervoy alone. The two-year OS rates were 64% for the Opdivo plus Yervoy combination, 59% for Opdivo alone and 45% for Yervoy alone. Results will be presented today in the press program and an oral presentation during the Update, Novel Indication, and New Immuno-oncology Clinical Trials session from 3:35 to 3:50 p.m. ET (Late-Breaking Abstract CT075) at the American Association for Cancer Research Meeting 2017 in Washington, D.C.

The updated safety data reported in this new analysis were consistent with previously reported experience, with no cumulative toxicity noted or new safety signals identified. Grade 3/4 treatment-related adverse events occurred in 58%, 21%, and 28% of the combination, Opdivo alone and Yervoy alone groups, respectively.

"It is encouraging to see such positive data from this trial, which further supports the scientific rationale to combine Immuno-Oncology agents as a potential treatment option for this aggressive form of melanoma. These CheckMate -067 survival data bolster our understanding of potential ways to combat untreated advanced melanoma and ultimately advance cancer care for patients," said James Larkin, Ph.D., FRCP, Consultant Medical Oncologist, Department of Medical Oncology, The Royal Marsden.

The proportion of patients experiencing complete responses (CR) compared to a previous 18 month follow-up analysis increased in the combination group to 17.2% from 12.1%, in the Opdivo alone group to 14.9% from 9.8%, and in the Yervoy alone group to 4.4% from 2.2%. Progression-free survival (PFS) and objective response rates (ORR) from updated analyses were both consistent with previous reports. The risk of disease progression was significantly reduced for both the combination and Opdivo monotherapy groups, 58% (HR 0.42; 95% CI: 0.34-0.51) and 46% (HR 0.54; 95% CI: 0.45-0.66), respectively, compared to Yervoy alone. The ORR for the two Opdivo groups, in combination and alone, and the Yervoy alone group was, respectively, 58.9% (95% CI: 53.3-64.4), 44.65% (95% CI: 39.1-50.3) and 19.0% (95% CI: 14.9-23.8).

"This first disclosure of overall survival data from CheckMate -067 helps to advance our understanding of the potential longer term benefits of Opdivo in combination with Yervoy in advanced melanoma, a cancer that historically has been difficult-to-treat," said Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb.

About CheckMate -067
CheckMate -067 is a Phase 3, double-blind, randomized trial that evaluated the combination of Opdivo plus Yervoy or Opdivo monotherapy versus Yervoy monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks (Q2W). Patients in the Opdivo monotherapy group (n=316) received Opdivo 3 mg/kg Q2W plus placebo. Patients in the Yervoy monotherapy group (n=315) received Yervoy 3 mg/kg every three weeks for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. OS and PFS were co-primary endpoints for the trial. Secondary endpoints included ORR, efficacy by tumor PD-L1 expression level and safety.

The Opdivo plus Yervoy combination and Opdivo monotherapy provided OS benefits across clinically relevant subgroups of patients versus Yervoy alone. Specifically, in patients with BRAF mutations, the combination reduced the risk of death 57% (HR 0.43; 95% CI: 0.28-0.66) and Opdivo monotherapy reduced the risk of death 40% (HR 0.60; 95% CI: 0.40-0.89) compared to Yervoy alone. In patients without BRAF mutations (Wild-type patients), the combination reduced the risk of death 38% (HR 0.62; 95% CI: 0.48-0.80) and Opdivo monotherapy reduced the risk of death 36% (HR 0.64; 95% CI: 0.49-0.83) compared to Yervoy alone. In patients with PD-L1 expression ≥5%, Opdivo in combination with Yervoy and Opdivo monotherapy resulted in a 40% (HR 0.60; 95% CI: 0.36-1.00) and 44% (HR 0.56; 95% CI: 0.34-0.90) reduction in risk of death, respectively, compared to Yervoy alone. In patients with PD-L1 expression <5%, the combination and Opdivo monotherapy resulted in a 45% (HR 0.55; 95% CI: 0.42-0.72) and a 35% (HR 0.65; 95% CI: 0.50-0.84) reduction in risk of death, respectively, compared to Yervoy alone.

The trial was not designed to statistically compare the two Opdivo groups. However, descriptive analyses found the combination treatment provided a relative reduction in the risk of death of 12% (HR 0.88; 95% CI: 0.69-1.12) when compared with Opdivo alone and reduced the risk of death for patients expressing PD-L1 <1% by 26% (HR 0.74; 95% CI: 0.52-1.06) and PD-L1 <5% by 16% (HR 0.84; 95% CI: 0.63-1.12) when compared to Opdivo alone. Survival between the two Opdivo containing groups was similar in patients expressing PD-L1 ≥1% (HR 1.03; 95% CI: 0.72-1.48) and PD-L1 ≥5% (HR 1.05; 95% CI: 0.61-1.83).

About Metastatic Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 87,000 new diagnoses of melanoma and more than 9,700 related deaths are estimated for 2017. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 388,262, with 98,288 related deaths. Melanoma is mostly curable when treated in its early stages. However, patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and 10-year survival of about 10% to 15%.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, China, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan, China.

About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.