FDA Expands Approval of Combination Therapy for Melanoma

Under accelerated approval based on progression-free survival (PFS), the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of patients with BRAFV600 wildtype and BRAFV600 mutation-positive unresectable or metastatic melanoma. This approval expands the original indication for the Opdivo plus Yervoy regimen for the treatment of patients with BRAFV600 wild-type unresectable or metastatic melanoma to include patients, regardless of BRAF mutational status, based on data from the Phase III CheckMate 067 trial in which PFS and overall survival were co-primary endpoints. FDA also expanded the use of Opdivo as a single agent to include previously untreated BRAF mutation-positive advanced melanoma patients. However, continued approval for this latter indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CheckMate 067, a double-blind, randomized study that evaluated the Opdivo plus Yervoy regimen or Opdivo monotherapy versus Yervoy monotherapy in patients with previously untreated advanced melanoma, including both BRAFV600 mutant and wild-type advanced melanoma, enrolled 945 patients who were randomized to receive the Opdivo plus Yervoy regimen (Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four doses followed by Opdivo 3 mg/kg every two weeks thereafter), Opdivo monotherapy (Opdivo 3 mg/kg every two weeks) or Yervoy monotherapy (Yervoy 3 mg/kg every three weeks for four doses followed by placebo every two weeks). Patients were treated until progression or unacceptable toxic effects. The median duration of exposure was 2.8 months for patients in the Opdivo plus Yervoy regimen with a median of four doses, and 6.6 months duration for the Opdivo monotherapy with a median of 15 doses.

Results demonstrated a statistically significant improvement in PFS in patients with advanced melanoma treated with the Opdivo plus Yervoy regimen and with Opdivo as a single agent versus Yervoy monotherapy. Median PFS was 11.5 months for the Opdivo plus Yervoy regimen and 6.9 months for Opdivo monotherapy, vs. 2.9 months for Yervoy monotherapy. The Opdivo plus Yervoy regimen demonstrated a 58 percent reduction in the risk of disease progression versus Yervoy, while Opdivo monotherapy demonstrated a 43 percent risk reduction versus Yervoy monotherapy. In addition, the Opdivo plus Yervoy regimen and Opdivo monotherapy demonstrated higher confirmed objective response rates versus Yervoy monotherapy.