The FDA has granted an accelerated approval to the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a treatment for patients with BRAF V600 wild-type unresectable or metastatic melanoma, based on findings from the phase 2 CheckMate-069 study.
In the double-blind study, the PD-1 inhibitor Opdivo plus the CTLA-4 inhibitor Yervoy reduced the risk of progression or death by 60 percent compared with Yervoy alone. With the combination, the objective response rate (ORR) was 60 percent compared with 11 percent with Yervoy alone in patients with BRAF wild-type melanoma.
The accelerated approval marks the first for an immunotherapy combination for patients with cancer, with an application for full approval pending with the FDA. This submission was based on the phase 3 CheckMate-067 study, which showed a 59 percent reduction in the risk of progression or death with the combination versus Yervoy alone. The FDA is scheduled to make a decision on this application by January 23.
“We are currently witnessing a turning point in cancer history, based on the significant impact immuno-oncology is making in the lives of patients with metastatic melanoma,” Tim Turnham, executive director, Melanoma Research Foundation, said in a statement. “Today’s approval of the first regimen of two immuno-oncology agents, Opdivo and Yervoy, is an exciting moment for our community because it reinforces we are on a positive path forward, providing new approaches which translate into meaningful results for patients.”
In the CheckMate-069 trial, 142 treatment-naïve patients with stage 3/4 melanoma were randomized in a two-to-one ratio to 3 mg/kg of Yervoy plus 1 mg/kg of Opdivo (95 patients) or placebo (47 patients) once every three weeks for four doses, followed by Opdivo at the same dose or placebo every two weeks until disease progression or unacceptable toxicity. Median patient age was 65 years, two-thirds of patients were males, and all but two patients had an ECOG performance status of 0 or 1.
Among patients with BRAF wild-type tumors (109 patients), median PFS was 8.9 months in the Opdivo/Yervoy group (72 patients) versus 4.7 months in the Yervoy arm (37 patients). In the study, similar PFS data were observed among patients with BRAF-positive melanoma (33 patients), at 8.5 versus 2.7 months in the combination (23 patients) and control (10 patients) arms, respectively.
The complete response rate with the combination was 17 percent versus none with monotherapy for patients with BRAF wild-type melanoma. Moreover, ORR with the combination was found to be independent of PD-L1 status. In PD-L1–positive and –negative tumors, respectively, ORR was 58 percent and 55 percent with Opdivo/Yervoy. In BRAF-positive patients, ORR was 52 percent versus 10 percent with the two-drug regimen versus monotherapy.
At six months, 79 percent of patients in the combination arm continued to respond to treatment. Of these patients, the median duration of response was less than nine months for 14 and greater than nine months for 20. The remaining nine patients had a duration of response ranging from three to seven months.