FDA Approves Expanded Indication for Metastatic Melanoma Combination

The FDA granted accelerated approved based on progression free survival (PFS) to an expanded indication for the combination therapy nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of metastatic melanoma.

The expanded indication is for patients with BRAF V600 wild-type mutation-positive unresectable or metastatic melanoma. The decision expands the original indication of the regimen for patients with BRAF V600 wild-type unresectable or metastatic melanoma to include patients regardless of BRAF mutational status.

The FDA also approved expanded use of Opdivo monotherapy to include patients with previously untreated BRAF mutation-positive advanced melanoma. The recent approval is significant after years of research to find better treatment options for patients with late stage melanoma.

“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,” said Head of US Commercial of Bristol-Myers Squibb, Chris Boerner. “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. To make this treatment option available to more patients is truly a milestone in the fight against this deadly disease.”

Continued approval for the expanded indication may be contingent upon verification and description of clinical benefit in future confirmatory trials, according to Bristol-Myers Squibb.

The phase 3 trial CheckMate-067, was double-blinded and randomized to evaluate Opdivo plus Yervoy combination regimen or Opdivo monotherapy and Yervoy monotherapy in patients with previously untreated advanced melanoma.

“Patients with metastatic melanoma historically have a very challenging disease,” said Jedd D. Wolchok, MD, PhD, chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center. “Recent advances in our understanding of the immune response to cancer has 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.”

The study evaluated 945 patients, including those with BRAF V600 mutation and wild-type advanced melanoma.

Patients were randomized to receive the Opdivo plus Yervoy regimen (Opdivo 1 mg/kg plus Yervoy 3 mg/kg every 3 weeks for 4 doses followed by Opdivo 3 mg/kg every 2 weeks thereafter; n=314), Opdivo monotherapy (Opdivo 3 mg/kg every 2 weeks; n=316), or Yervoy monotherapy (Yervoy 3 mg/kg every 3 weeks for 4 doses followed by placebo every 2 weeks; n=315).

The trial showed a statistically significant improvement in PFS among patients treated with the Opdivo plus Yervoy Regimen (p<0.0001) and with Opdivo monotherapy (p<0.0001) compared with Yervoy monotherapy.

The Opdivo plus Yervoy regimen showed median PFS at 11.5 months (95% CI: 8.9-16.7), while PFS with the Opdivo monotherapy was 6.9 months (95% CI: 4.3-9.5) compared with 2.9 months (95% CI: 2.8-3.4) with Yervoy monotherapy.

Furthermore, the combination regimen showed a 58% reduced disease progression risk compared with Yervoy (HR: 0.42; 95% CI: 0.34-0.51; p<0.0001). Single-agent Opdivo showed a 43% reduced risk compared with Yervoy monotherapy (HR: 0.57; 95% CI: 0.47-0.69; p<0.0001).

“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 2 Immuno-Oncology treatments available to more patients fighting this disease,” said Tim Turnham, executive director of the Melanoma Research Foundation.