The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for treating patients with BRAF V600 wild-type unresectable or metastatic melanoma, the agency and manufacturer Bristol-Myers Squibb announced. It is the first FDA-approved anticancer treatment involving the combination of two immunotherapy agents.
The FDA approved the combination therapy under its accelerated approval program based on durable tumor response rates reported for the pivotal phase II, double-blind, randomized CheckMate-069 trial.
CheckMate-069 enrolled 140 previously untreated patients diagnosed with advanced unresectable or metastatic melanoma; 109 of whom had BRAF wild-type tumors. The study found a significantly increased confirmed objective response rates among patients with BRAF wild-type melanoma who were treated with the nivolumab plus ipilimumab regimen compared to outcomes for ipilimumab monotherapy (60% vs 11%; P < .001).
Complete responses were reported for 17% of patients and partial responses for 43% of patients administered nivolumab plus ipilimumab. The combination immunotherapy regimen was associated with a median progression-free survival of 8.9 months versus 4.7 months for ipilimumab alone, Bristol-Myers Squibb reported.
“This trial provides clinical rationale for targeting the immune system with two immuno-oncology agents in metastatic melanoma,” the company announced. Continued FDA approval for nivolumab plus ipilimumab for advanced melanoma “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to a Bristol-Myers Squibb press release.
Patients administered the nivolumab-ipilimumab combination regimen experienced more grade 3/4 adverse reactions (69%) than patients in the ipilimumab monotherapy group (43%), and a higher rate of discontinuation of treatment (43% vs 11%) and dose delay (47% vs 22%), the company reported. Serious adverse reactions occurred in 62% versus 39% of patients taking the combination and monotherapy, respectively.
The most common toxicities leading to discontinuation of nivolumab were colitis (16%), diarrhea not treated with corticosteroids (4%), increased ALT levels (4%), pneumonitis (3%), and AST increase (3%).
“Historically, metastatic melanoma has been a difficult disease to treat,” said Jedd D. Wolchok, MD, PhD, Chief of Melanoma and Immunotherapeutics Service at the Memorial Sloan Kettering Cancer Center in New York. “Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab (Yervoy) in metastatic melanoma.”
Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor and ipilimumab is a CTLA-4 immune checkpoint inhibitor. Both agents improve immune antitumor activity.