FDA approves Opdivo + Yervoy combined with limited chemotherapy as first-line treatment of metastati

Bristol Myers Squibb announced that Opdivo (nivolumab) 360 mg plus Yervoy (ipilimumab) 1 mg/kg (injections for intravenous use) given with two cycles of platinum-doublet chemotherapy was approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.

The therapy is approved for patients with squamous or non-squamous disease and regardless of PD-L1 expression. This application was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible. On May 15, the FDA approved Opdivo + Yervoy as a first-line treatment for certain patients with metastatic NSCLC whose tumors express PD-L1≥1% as determined by an FDA-approved test.

Approval for Opdivo + Yervoy with limited chemotherapy is based on the pre-specified interim analysis from the Phase 3 CheckMate -9LA trial in which Opdivo + Yervoy combined with two cycles of platinum-doublet chemotherapy demonstrated superior overall survival (OS) versus chemotherapy (hazard ratio [HR] 0.69; 96.71% confidence interval [CI]: 0.55 to 0.87; P=0.0006) regardless of PD-L1 expression or tumor histology (minimum 8.1 months follow up).1,3 Median overall survival (mOS) was 14.1 months (95% CI: 13.2 to 16.2) versus 10.7 months (95% CI: 9.5 to 12.5), respectively.1 In a follow-up analysis at 12.7 months, the hazard ratio improved numerically to 0.66 (95% CI: 0.55 to 0.80), with mOS of 15.6 months (95% CI: 13.9 to 20.0) and 10.9 months (95% CI: 9.5 to 12.5).1,3 At one year, 63% of patients treated with Opdivo + Yervoy with limited chemotherapy and 47% of those treated with chemotherapy were still alive.

Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion-related reactions; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

“We have come a long way in understanding the role of dual immunotherapy-based approaches in cancer and the potential impact on patients’ long-term outcomes,” said David P. Carbone, MD, PhD, CheckMate -9LA investigator and Director of the James Thoracic Oncology Center at The Ohio State University. “The positive findings from CheckMate -9LA demonstrate the benefit of combining dual immunotherapy with limited chemotherapy for NSCLC patients regardless of PD-L1 status. With today’s approval, more patients now have access to an Opdivo + Yervoy-based option and a chance at a longer life.”

In the trial, the overall response rate (ORR) per Blinded Independent Central Review (BICR) was 38% (95% CI: 33 to 43) for patients treated with Opdivo + Yervoy with limited chemotherapy and 25% (95% CI: 21 to 30) for patients treated with chemotherapy.

“Non-small cell lung cancer is a complex disease that requires multiple treatment options to address the needs of different patient populations,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. “This second approval of an Opdivo + Yervoy-based combination for the first-line treatment of advanced NSCLC now gives more patients access to a dual immunotherapy approach that can be administered with or without limited chemotherapy, depending on the patient and their PD-L1 status, and the possibility of a chance to live longer.”

Opdivo + Yervoy is a unique combination of immune checkpoint inhibitors, featuring a potentially synergistic mechanism of action that targets two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells: Yervoy helps activate and proliferate T cells, while Opdivo helps existing T cells discover the tumor. Some of the T cells stimulated by Yervoy can become memory T cells, which may allow for a long-term immune response. Targeting of normal cells can also occur and result in immune-mediated adverse reactions, which can be severe and potentially fatal.

“Receiving a diagnosis of advanced lung cancer is devastating,” said Andrea Ferris, president and chief executive officer, LUNGevity. “Today’s announcement is welcome news as it provides a new dual immunotherapy-based option for previously untreated patients searching for a treatment that may help extend their lives.”

This application is part of the FDA’s Project Orbis initiative, enabling concurrent review by the FDA and the health authorities in Australia, Canada and Singapore.