Long-Term Follow-up of Phase I Nivolumab Trial

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F. Stephen Hodi, Jr, MD

Michael B. Atkins, MD

Patients who experience an immune-related–type response [on nivolumab] can have overall survival outcomes similar to those with RECIST responses.

—F. Stephen Hodi, Jr, MD

In the longest follow-up to date of any programmed death (PD)-1 receptor inhibitor in previously treated advanced melanoma, one-third of patients are demonstrating durable responses to the investigational agent nivolumab, and in some cases, these persist following discontinuation of the drug, according to F. Stephen Hodi, Jr, MD, Director of the Melanoma Center and Director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute, Boston.

CA209-003 Trial

“Of 107 patients, 47 are still alive, with a median follow-up of 22 months and a range of 14 to 51 months,” Dr. Hodi reported at the 2014 ASCO Annual Meeting.1

Dr. Hodi presented the long-term follow-up of CA209-003 study of nivolumab monotherapy in 107 advanced melanoma patients. At a dose of 3 mg/kg every 2 weeks, the objective response rate was 41%, and median duration of response was 75 weeks. This is the dose selected for phase III studies, he said.

Patients receiving this dose of nivolumab had a median progression-free survival of 9.7 months and median overall survival of 20.3 months. Responses were ongoing in 19 of 34 (56%) responders at the time of analysis, and 11 of the 21 (52%) responding patients who discontinued the drug for reasons other than progression continued to respond for 24 weeks or longer. Of these 11, 7 (64%) remained in response for up to 56 weeks. Nearly half the responding patients showed a response at the first tumor assessment at 8 weeks, he added.

The median overall survival was 17.3 months, and overall survival rates were 63% at 1 year, 48% at 2 years, and 41% at 3 years, Dr. Hodi reported.

Ten patients demonstrated an immune-related type of response, which was defined as ≥ 30% reduction in targeted lesions from baseline or after initial progression disease, or patients with progression disease for at least three tumor assessments, with a best change in tumor burden of ≤ 20% from baseline.

“Patients who experience an immune-related–type response can have overall survival outcomes similar to those with RECIST responses,” Dr. Hodi noted. At 42 weeks, almost 80% of both these subsets remained alive.

Activity was seen across patient populations and prognostic factors. No new safety signals were observed.

Pidilizumab Phase II Trial

Another investigational anti–PD-1 agent, pidilizumab, produced a more modest response rate, 5% to 6%, than has come to be expected from this emerging class of immune checkpoint inhibitors. The phase II open-label randomized trial of patients was reported by Michael B. Atkins, MD, Deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC, and Professor of Oncology and Medicine at Georgetown University School of Medicine.2

“The study missed the primary endpoint of objective response rate but met the secondary endpoint of overall survival,” Dr. Atkins reported. At 12 months, 64.5% of patients remained alive.

Dr. Atkins noted that “despite the low response rate, the 12-month survival in heavily pretreated patients appears to be better than anticipated and similar to that reported for other anti–PD-1 antibodies.”

The 12-month survival rate was 64.5%, compared to 46% for ipilimumab ­(Yervoy), 62% for nivolumab, and 81% for pembrolizumab, Dr. Atkins noted.

The survival rate was approximately 80% for the 57% of patients who were treated after the study with ipilimumab, or who achieved stable disease or better with prior ipilimumab exposure, he added. n

Disclosure: Dr. Hodi is an unpaid consultant for and has received clinical trial support (via his institution) from Bristol-Myers Squibb, and has a licensing agreement with Bristol-Myers Squibb as per institutional policy. Dr. Atkins has provided expert testimony for CureTech and has served on advisory boards for Bristol-Myers Squibb, Merck, Genentech, GlaxoSmithKline, Pfizer, and Prometheus. For full disclosures of all the study authors, visit ■


1. Hodi FS, Sznol M, Kluger HM, et al: Long-term survival of ipilimumab-naive patients with advanced melanoma treated with nivolumab in a phase 1 trial. ASCO Annual Meeting. Abstract 9002. Presented June 2, 2014.

2. Atkins MB, Kudchadkar RR, Sznol M, et al: Phase 2, multicenter, safety and efficacy study of pidilizumab in patients with metastatic melanoma. ASCO Annual Meeting. Abstract 9001. Presented June 2, 2014.