CHICAGO—Nivolumab produced durable overall survival and responses in a large cohort of patients with stage IV melanoma, according to long-term follow-up results of a phase 1 study reported at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“I think nivolumab is a real breakthrough drug for patients with metastatic melanoma, and probably for other diseases, too,” said lead author Mario Sznol, MD, a professor of medical oncology at the Yale Cancer Center in New Haven, CT. “The high level of activity observed with this drug opens up a number of avenues for future research to understand and challenge the ways tumors evade the immune system. We‘re very excited that there is potential for even more activity in combination with other drugs.”

Historically, response rates to immunotherapy drugs in advanced melanoma are 5% to 10%; however, in this study, 30% of patients experienced tumor shrinkage. Patients were heavily pretreated; 25% had three or more prior therapies and 63% had two or more.

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As of July 2012, 107 patients with previously treated melanoma received 12 cycles or fewer (four doses/cycle) of nivolumab intravenously every 2 weeks until discontinuation criteria were met. Cohorts of patients were expanded at 0.1, 0.3, 1, 3, and 10 mg/kg.

Median patient age was 61 years (range, 29-85 years); 67% were male, and 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 78% had visceral site metastases and 36% had elevated lactate dehydrogenase. A total of 66% had received two or more prior therapies and 25%, three or more prior therapies, including immunotherapy, interleukin-2, or a BRAF inhibitor.

Overall response rates (ORRs) were observed at all doses, with the highest, 41% (including one complete response) at 3 mg/kg; 33 (31%) of patients experienced tumor shrinkage of at least 30% and seven (7%) had a stable disease rate of 24 weeks or longer, with a median duration of response of 104 weeks (range, 18.4–117.0+ weeks). As of March 2013, 19 (58%) of the responding patients continued to respond.

For 17 responding patients who discontinued therapy for reasons other than disease progression, 12 (71%) responded for 16 weeks or longer since the end of therapy. An additional eight (67%) of 12 patients remained in response from 16 to 56 weeks at the time of data analysis.

Median progression-free survival (PFS) was 3.7 months; 1-year PFS was 36% and 2-year PFS, 27%. Across doses, median overall survival (OS) was 16.8 months (95% CI: 12.5–31.6 months); 1-year OS was 62% and 2-year OS, 43%. A total of 47 patients were still alive with a median overall follow-up of 22 months and a range of 14 to 51 months. At the 3 mg/kg dose selected for phase 3 trials, median OS was 20 months and median PFS, 9.7 months.

Nivolumab was well tolerated and no new safety signals or drug-related pneumonitis deaths were observed.

“While this was not a randomized clinical trial, it had a considerable number of patients and the durability of responses is a sign of very promising clinical activity,” said Dr. Sznol. Another reassuring point, he added, is that patients in this clinical trial are representative of those with advanced melanoma; that is, the investigators did not select for the very best patients. Three ongoing randomized phase 3 trials in treatment-naïve or previously treated patients with melanoma are ongoing.

This research was supported by Bristol-Myers Squibb.