FDA accelerates approval of melanoma drug

Jan 02, 2015, 5:00am

The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of unresectable or metastatic melanoma and for patients whose disease has progressed following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor.

The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of unresectable or metastatic melanoma and for patients whose disease has progressed following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor.

According to the FDA, approval was based on objective response rate (ORR) and durability of response in the first 120 patients who were treated with nivolumab and had a minimum six-months follow-up as part of a trial in which 370 patients with unresectable or metastatic melanoma received nivolumab intravenously every two weeks or investigator’s choice of chemotherapy, which included either dacarbazine or the combination of carboplatin plus paclitaxel. Patients with unresectable or metastatic melanoma were required to have disease progression following ipilimumab, and a BRAF inhibitor if BRAF V600 mutation-positive. Patients with either an autoimmune disease, a medical condition that required corticosteroids or immunosuppression, or a history of severe ipilimumab-related adverse reactions were excluded from the trial.

The major efficacy endpoints were confirmed ORR-assessed by a blinded independent review committee-and response duration. The ORR was 32 percent, with four complete responses and 34 partial responses. Five responding patients have progressed, while the remaining 33 patients have ongoing responses (range 2.6 to 10-plus months). Thirteen patients have ongoing responses of six months or longer.

The most common adverse reaction among the 268 patients receiving nivolumab was rash. The most frequent Grade 3 and 4 adverse drug reactions, observed in 2 percent to less than 5 percent with nivolumab, were abdominal pain, hyponatremia, increased aspartate aminotransferase and increased lipase. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, nephritis/renal dysfunction, hypothyroidism and hyperthyroidism.

Among those applauding the FDA’s action was the Melanoma Research Alliance (MRA).

“The approval . . . is the latest in a string of good news for patients in 2014 and provides yet another weapon in the fight against melanoma,” MRA Chief Science Officer Louise M. Perkins, Ph.D., tells Dermatology Times. “Dermatologists and their patients with aggressive metastatic melanoma now have more effective options available, and the future looks promising that early-stage patients could potentially benefit, as well.”

As a condition of the accelerated approval, the FDA requires Bristol-Myers Squibb to conduct multicenter, randomized trials establishing the superiority of nivolumab over standard therapy in adult patients with unresectable or metastatic melanoma to verify and describe the clinical benefit of the drug.