Bristol-Myers Squibb Company, a global biopharmaceutical company,  announced that the US Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection, for intravenous use, for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

This announcement marks the approval of the first and only PD-1 inhibitor to deliver significant overall survival (OS) in patients with advanced RCC who have received prior anti-angiogenic therapy.1 In the CheckMate -025 trial, patients treated with Opdivo achieved a median OS of 25 months (95% CI: 21.7-not estimable [NE]) versus 19.6 months (95% CI: 17.6-23.1) for everolimus, a current standard of care (SOC) in this patient population (hazard ratio [HR]: 0.73; [95% CI: 0.60-0.89; p=0.0018]), based on a prespecified interim analysis. In the study, the safety profile was consistent with prior Opdivo studies.

“This is the fifth approval for Opdivo across three distinct tumor types. This latest approval reflects our commitment to delivering on our promise to provide cancer patients with a potential for long-term survival,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer at Bristol-Myers Squibb. “We believe our pioneering approach to Immuno-Oncology is driving change in how cancer may be treated.”

Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; and embryofetal toxicity.

The US approval was based on data from CheckMate -025, an open-label, randomized phase 3 study which demonstrated a median OS benefit of 25 months (95% CI: 21.7-NE) compared with 19.6 months (95% CI: 17.6-23.1) for everolimus (HR: 0.73; [95% CI: 0.60-0.89; p=0.0018]). This is the first time an immune checkpoint inhibitor has delivered a significant survival benefit in this patient population.1 On September 16, 2015, the FDA granted Breakthrough Therapy Designation to Opdivo for advanced RCC patients treated with prior anti-angiogenic therapy, also based on positive results from the CheckMate -025 study, reinforcing the unmet need in the treatment of RCC.

“As an Immuno-Oncology agent that works directly with the body’s immune system, Opdivo offers a new approach for physicians to use when treating patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy,” continued Cuss. “For the first time, these patients have a PD-1 inhibitor treatment option, which has the potential to provide an unprecedented survival advantage compared to a standard of care.”

CheckMate -025 is a landmark, open-label, randomized phase 3 study, evaluating Opdivo compared to an active comparator (everolimus) in patients with advanced RCC who have received prior anti-angiogenic therapy. Clinical results from CheckMate -025 were recently presented at the 2015 European Cancer Congress with simultaneous publication in The New England Journal of Medicine.

In CheckMate -025, 821 patients were randomized to receive Opdivo (3 mg/kg administered intravenously every two weeks; n=410) compared to a SOC (everolimus, 10 mg administered orally daily; n=411). The primary endpoint was OS. Objective response rate (ORR) was evaluated as a secondary endpoint. The prespecified interim analysis was conducted when 398 events were observed (70% of the planned number of events for final analysis). In this trial, Opdivo demonstrated a median OS of 25 months (95% CI: 21.7-NE) versus 19.6 months (95% CI: 17.6-23.1) for everolimus (HR: 0.73; [95% CI: 0.60-0.89; p=0.0018]), offering a 5.4 month survival benefit. With Opdivo, the OS benefit was observed independent of PD-L1 expression. In addition to improving survival, Opdivo demonstrated a superior ORR compared to everolimus (21.5%; 95% CI: 17.6–25.80 vs. 3.9%; 95% CI: 2.2–6.2) with a higher median duration of response (23.0 months; 95% CI: 12.0-NE vs. 13.7 months; 95% CI: 8.3-21.9).

“Results from CheckMate -025 mark the first time an Immuno-Oncology treatment has demonstrated a survival advantage in patients with advanced renal cell carcinoma compared to a standard of care in this population,” said Robert J. Motzer, M.D., medical oncologist, Memorial Sloan Kettering Cancer Center. “For patients with advanced renal cell carcinoma, treatment options are limited and new approaches that extend survival are desperately needed. With the FDA approval of Opdivo, the kidney cancer community is now a step closer toward achieving long-term survival, which has remained elusive for many patients. This represents a true shift in our treatment paradigm.”

While the treatment landscape for RCC has improved over the last decade, patients are in need of new treatment options that demonstrate longer-term effects and overall survival benefits.

“This approval of Opdivo represents a major milestone for the kidney cancer community,” said William P. Bro, chief executive officer and patient coordinator, Kidney Cancer Association. “We thank Bristol-Myers Squibb and the FDA for working swiftly to bring this important new treatment option and potential for extended survival to patients.”

The safety profile of Opdivo in CheckMate -025 was consistent with prior studies. Serious adverse events occurred in 47% of patients receiving Opdivo.1 The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In the study, the most common adverse reactions (=20%) reported in patients receiving Opdivo versus everolimus were asthenic conditions (56% vs. 57%), cough (34% vs. 38%), nausea (28% vs. 29%), rash (28% vs. 36%), dyspnea (27% vs. 31%), diarrhea (25% vs. 32%), constipation (23% vs. 18%), decreased appetite (23% vs. 30%), back pain (21% vs. 16%), and arthralgia (20% vs. 14%).

Bristol-Myers Squibb is a pioneer in the field of cancer research and treatment known as Immuno-Oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor, and works by targeting the immune system through the PD-1 immune checkpoint pathway.1 Targeting the immune system through this pathway is now recognized as a new approach to RCC treatment.3

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as a monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.