ASCO 2014: PD-1–Targeting Antibody Pembrolizumab Produces Long-Term Responses in Patients With Metastatic Melanoma
Findings from a large phase I study of 411 patients with advanced melanoma show that the PD-1–targeting antibody pembrolizumab (MK-3475) produced responses in 34% of patients, including 28% of patients whose disease progressed on prior treatment with ipilimumab (Yervoy). Among those who responded to pembrolizumab, 88% had ongoing responses at a median follow-up of 12 months.
“We were excited to see that pembrolizumab was effective in previously untreated patients as well as in those who had multiple prior therapies, including ipilimumab,” said lead study author Antoni Ribas, MD, PhD, Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “These are early data, but they tell us we are on to something really important.” Dr. Ribas presented the findings at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA9000^).
Activity Across All Subgroups
Pembrolizumab is an investigational, selective, humanized monoclonal anti–PD-1 antibody, designed to block the interaction of PD-1 on T cells and reactivate antitumor immunity. Data on the first 135 patients were presented at last year’s Annual Meeting, showing a 41% response rate. This year’s update, based on 411 patients with metastatic melanoma, is “the largest phase I clinical trial ever done in this disease,” Dr. Ribas noted at the ASCO press briefing on progress in immunotherapy.
The study included seven different cohorts with different eligibility and three different dosing regimens for single-agent pembrolizumab. Activity was observed across all dose levels and patient subgroups, irrespective of prior ipilimumab therapy, performance status, LDH levels, BRAF mutation status, tumor stage, and number and type of prior therapies.
Durable Responses
Overall, 34% of patients experienced tumor response, as assessed by Independent Review. This included 40% of the 190 patients not previously treated with ipilimumab and 28% of the 221 patients whose disease progressed on prior ipilimumab. “This is a remarkably high response rate for an antibody that hits the immune system and not the tumor directly,” Dr. Ribas said.
At the time of analysis (October 2013), 88% of reported responses were ongoing. Duration of responses ranged from 6 to 76 weeks, and median response duration had not yet been reached.
The estimated 1-year survival rate among all 411 patients in the study was 69% percent. At 1.5 years, the estimated overall survival rate was 62% and median overall survival duration was not reached, Dr. Ribas reported. The estimated 1-year survival rate was 74% percent in patients receiving pembrolizumab who had not previously treated with ipilimumab and 65% in patients who had received prior ipilimumab therapy.
‘One of the Most Benign Therapies’
“This is one of the most benign therapies I’ve ever used in my clinic,” Dr. Ribas said. The most common adverse events of any grade were fatigue, pruritus, and rash, but neither these nor any other specific adverse event affected more than 1% to 2% of patients. Only 4% of patients discontinued treatment due to a drug-related side effect.
“The remarkable thing is that almost 90% of these patients are having durable responses with a toxicity profile that is almost unheard of in metastatic cancer—10% or 12%. This is really extraordinary about this class of drugs,” remarked Steven O’Day, MD, Clinical Professor of Medicine at the University of Southern California, Keck School of Medicine, Los Angeles, and moderator of the ASCO press briefing on progress in immunotherapy.
The Food and Drug Administration had previously granted a Breakthrough Therapy designation to pembrolizumab for advanced melanoma. In May 2014, the FDA granted pembrolizumab a Priority Review designation under its Accelerated Approval program. Ongoing randomized controlled studies are assessing the efficacy and safety of pembrolizumab in advanced melanoma patients not previously treated with ipilimumab and in those with disease progression on or after ipilimumab. Studies in an adjuvant setting are planned.
This research was supported by Merck. Dr. Ribas reported a consultant or advisory role with Amgen, GlaxoSmithKline, Merck, and Genentech, stock ownership with Kite Pharma, and a position as an advisory board member and/or consultant of the trial sponsor. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
