European Commission approves Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) for first-line treatment of patients with intermediate- and poor-risk advanced renal cell carcinoma

Bristol-Myers Squibb Company (NYSE: BMY) announced that the European Commission has approved the combination of Opdivo (nivolumab) 3 mg/kg plus Yervoy (ipilimumab) 1 mg/kg ("low-dose") for the first-line treatment of patients with intermediate- and poor-risk advanced renal cell carcinoma (RCC). This decision represents the first approval of an Immuno-Oncology (I-O) combination therapy for patients with this type of cancer in the European Union.

"Currently, less than 50% of patients with metastatic renal cell carcinoma survive beyond two years, and there is almost no complete remission observed, which underscores the need for new treatments for this disease," said Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Institut Gustave Roussy. "Today's approval offers patients in the European Union a first-line treatment option that has demonstrated a complete response rate of almost 10% and a significant improvement in overall survival with fewer Grade 3 and 4 adverse reactions compared to sunitinib."

The approval is based on results from the Phase 3 CheckMate -214 clinical trial, which was stopped early following a planned interim analysis that showed that the combination of Opdivo plus low-dose Yervoy demonstrated a significant increase in overall survival (OS), with a 37% decreased risk of death in intermediate- and poor-risk patients compared to a current standard of care, sunitinib (Hazard Ratio [HR] 0.63; 99.8% Confidence Interval [CI]: 0.44 to 0.89; p<0.0001). The OS benefit was observed regardless of PD-L1 expression level. Median OS in patients treated with Opdivo plus low-dose Yervoy was not yet reached (95% CI: 28.2 to not estimable [NE]), compared to 25.9 months for patients treated with sunitinib.

Opdivo plus low-dose Yervoy also demonstrated a higher objective response rate of 41.6% (95% CI: 36.9 to 46.5; p<0.0001; n=177/425) versus 26.5% for sunitinib (95% CI: 22.4 to 31.0; n=112/422) and a complete response rate of 9.4% for the Opdivo plus low-dose Yervoy cohort versus 1.2% for the sunitinib arm. Among patients who responded, median duration of response in patients treated with Opdivo plus low-dose Yervoy was not yet reached (95% CI: 21.8 to NE) compared to 18.2 months for sunitinib (95% CI: 14.8 to NE). The combination of Opdivo plus low-dose Yervoy was also associated with fewer overall Grade 3 or 4 adverse events compared to sunitinib (65% versus 76%).

"We are extremely pleased that the European Commission has approved Opdivo plus low-dose Yervoy based on the significant survival benefit demonstrated in the CheckMate -214 trial," said Chris Boerner, Chief Commercial Officer, Bristol-Myers Squibb. "Today's approval helps further our goal of transforming the way cancer is treated and increasing quality, long-term survival for patients."

About CheckMate -214

CheckMate -214 is a Phase 3, randomized, open-label study evaluating the combination of Opdivo 3 mg/kg plus Yervoy 1 mg/kg versus sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC). In the intermediate- and poor-risk study population, 425 patients received Opdivo 3 mg/kg plus Yervoy 1 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg every two weeks, and 422 patients received sunitinib 50 mg once daily for four weeks, followed by two weeks off every cycle. The recommended dosing for the Opdivo plus low-dose Yervoy combination is Opdivo 3 mg/kg followed by Yervoy 1 mg/kg each infused intravenously over 30 minutes on the same day every three weeks for four doses. After completing four doses of the combination, Opdivo should be administered intravenously 240 mg every two weeks over 30 minutes or 480 mg every four weeks over 60 minutes until disease progression or unacceptable toxicity.

The co-primary efficacy outcome measures of the trial were overall survival, objective response rate (Complete Response + Partial Response) and progression-free survival as determined by an independent radiographic review committee (IRRC) in intermediate- and poor-risk patients. Patients were included regardless of their PD-L1 status.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 140,000 deaths worldwide each year. Clear-cell RCC is the most prevalent type of RCC and constitutes 80% to 90% of all patients. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 8%.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients with cancer and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research, to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and immune system. We source innovation internally and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

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 65 countries, including the United States, the European Union, Japan and China. 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.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., 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, Ono and Bristol-Myers Squibb 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.

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