Bristol-Myers Squibb Company recently announced that the U.S. Food and Drug Administration (FDA) has approved the combination regimen of Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma.
“The melanoma community is excited to see the ongoing developments in research from the pharmaceutical industry, including Bristol-Myers Squibb, who made the first approved combination of two Immuno-Oncology treatments available to more patients fighting this disease,” Tim Turnham, the Melanoma Research Foundation’s executive director, said in a press release. “Today’s expanded approvals continue to bring new treatment options to patients, and demonstrate the ongoing impact of Immuno-Oncology research.”
Metastatic melanoma is the most damaging form of this malignancy, which occurs when cancer spreads beyond the skin surface to other organs. Cancer cells can take advantage of ‘regulatory’ pathways, which work as checkpoints, to remain unidentified by the immune system, and protect the tumor from an immune attack. Both Opdivo (nivolumab) and Yervoy (ipilimumab) are immune checkpoint inhibitors that target distinct, separate and complementary checkpoint pathways (PD-1 and CTLA-4, respectively). Yervoy’s inhibiting of CTLA-4 has been shown to augment T-cell activation and proliferation, while Opdivo restores the active T-cell response directed at the tumor. The mechanism of action involves dual immune checkpoint inhibition resulting in increased anti-tumor activity, but this process may affect healthy cells and end in immune-mediated adverse reactions.
This accelerated approval expands the original indication for Opdivo/Yervoy to treat patients with BRAF V600 wild-type unresectable or metastatic melanoma regardless of BRAF mutational status, based on data from the Phase 3 CheckMate-067 trial, in which progression-free survival (PFS) and overall survival (OS) were co-primary endpoints. The indication now grounds itself on PFS. The continuation of this indication’s approval may be contingent upon verification of clinical benefits in confirmatory clinical trials.
“For nearly a decade, our researchers have worked tirelessly to find treatment options that could improve outcomes for patients with late-stage melanoma, a particularly aggressive cancer, and we are incredibly proud of today’s approval to expand the use of the Opdivo + Yervoy Regimen to include patients with BRAF mutation-positive unresectable or metastatic melanoma. CheckMate -067 is the first Phase 3 study to observe the efficacy and safety of both Opdivo as a single-agent as well as in combination with Yervoy versus Yervoy alone,” said Chris Boerner, Bristol-Myers Squibb’s Head of U.S. Commercial. “To make this treatment option available to more patients is truly a milestone in the fight against this deadly disease.”
Opdivo was also approved for expanded use as a single-agent therapy to include previously untreated BRAF mutation-positive advanced melanoma. Its use in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma is based on PFS and may be contingent upon verification of clinical benefit in confirmatory trials.
“Patients with metastatic melanoma historically have a very challenging disease. Recent advances in our understanding of the immune response to cancer have yielded therapies which provide meaningful responses and hope. The combination of two Immuno-Oncology treatments, nivolumab and ipilimumab, has been shown to provide these patients with a much needed improvement in progression-free survival and response rates,” said Jedd D. Wolchok, MD, PhD, chief of the Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center. “This expanded approval for the nivolumab and ipilimumab regimen provides more advanced melanoma patients with an Immuno-Oncology combination treatment, and the potential for improved outcomes.”
CheckMate-067 is a Phase 3, double-blind, randomized study evaluating Opdivo and Yervoy as a combination therapy — versus either drug as a monotherapy — in 945 patients with previously untreated advanced melanoma. Its primary endpoints are PFS and OS; the study is ongoing and patients continue to be followed for OS.