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FDA Grants Accelerated Approval for Melanoma Drug Opdivo (Nivolumab)

Treatment indicated for patients who have progressed on Yervoy

The FDA has approved Opdivo (nivolumab, Bristol-Myers Squibb) injection for intravenous use.

Nivolumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression after treatment with Yervoy (ipilimumab, Bristol-Myers Squibb) and, if BRAF V600 mutation-positive, a BRAF inhibitor. This indication is approved under an accelerated approval based on the tumor response rate and the durability of response. Continued approval for this indication may be contingent on verification and the description of clinical benefit in confirmatory trials.

Metastatic melanoma is the deadliest form of skin cancer, and despite recent advances, limited treatment options are available for patients who have been previously treated with approved agents.

Nivolumab is associated with immune-mediated pneumonitis, colitis, hepatitis, nephritis, renal dysfunction, hypothyroidism, hyperthyroidism, and embryofetal toxicity, among other adverse reactions.

Shipments of the drug are expected to begin within 1 to 2 weeks.

Nivolumab is the only PD-1–blocking antibody that has been shown to be effective in a pivotal, phase III clinical trial (CheckMate-037) in patients with advanced melanoma who had progressed on ipilimumab and, if BRAF mutation-positive, a BRAF inhibitor. The efficacy of nivolumab was evaluated in a single-arm, non-comparative planned interim analysis of the first 120 patients who received the drug with a minimum of 6 months follow-up in the CheckMate-037 study.

CheckMate -037 was a randomized trial comparing nivolumab 3 mg/kg (n = 268), administered every 2 weeks, with chemotherapy (n = 102), which consisted of the investigator’s choice of either single-agent dacarbazine 1,000 mg/m2 every 3 weeks or the combination of carboplatin AUC 6 every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks, in patients with advanced melanoma who had been previously treated with and had progressed on ipilimumab and, if BRAF mutation-positive, a BRAF inhibitor. No premedication is required with nivolumab.

The study’s primary endpoint was the objective response rate (ORR).

In the interim analysis of nivolumab-treated patients (n=120), 76% had M1C disease; 18% had a history of brain metastases; and 56% had elevated LDH levels. The patients’ median age was 58 years, and 22% were BRAF V600 mutation-positive.

Nivolumab achieved a 32% response rate (38/120) with a dosing strength and frequency of 3 mg/kg intravenously over 60 minutes every 2 weeks. Four patients (3%) showed a complete response, and 34 (28%) showed a partial response. Of the 38 patients with responses, 33 (87%) had ongoing responses, with durability of response ranging from 2.6+ to 10+ months, which included 13 patients with ongoing responses of 6 months or longer. Responses to nivolumab were demonstrated in patients with or without the BRAF mutation.

In the CheckMate-037 trial, serious adverse events (AEs) occurred in 41% of the patients treated with nivolumab. The most frequent grade-3 and grade-4 AEs (reported in 2% to less than 5% of patients receiving nivolumab) included abdominal pain, hyponatremia, increased aspartate aminotransferase (AST), and increased lipase. The most common AE reported with nivolumab was rash (21%).

Source: Bristol-Myers Squibb; December 22, 2014.

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