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New Study Shows Efficacy of Combination Immunotherapy Regimen for Advanced Melanoma

August 24, 2021

Results from a clinical trial investigating the use of pembrolizumab, an anti-PD-1 agent, in combination with ipilimumab, a CTLA4 inhibitor, for the treatment of advanced melanoma showed safety and efficacy in a cohort of 70 patients.

Findings from the multicenter study1 were initially published online in June 2021 in the Journal of Clinical Oncology, along with an accompanying editorial2. This is the first clinical trial in refractory melanoma to test the safety and efficacy of combining ipilimumab in a low dose with pembrolizumab after the initial failure of anti-PD-1/Li therapy. 

Based on these results, the National Comprehensive Cancer Center melanoma guideline panel endorsed this treatment approach in November 2020 as a standard of care option for patients in general oncology practice.

Jason J. Luke, MD, FACP, associate professor of medicine and director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, conceived of, designed, and was the principal investigator for the clinical trial which was funded as a grant through the Merck Investigator Studies Program. Dr. Luke was the manuscript’s senior author.

Study Overview and Clinical Findings Highlights

This study enrolled patients from seven centers in the United States between December 2016 and November 2019 with advanced melanoma whose disease had progressed after initial immunotherapy with anti-PD-1 agents or non-anti-CTLA-4 therapy. Initially, 35 patients were enrolled in the study. When the initial cohort was deemed to have the primary endpoint of the trial, the enrollment was expanded to include a total of 70 individuals.

Participants were given doses of ipilimumab at the rate of 1 mg/kg in combination with 200 mg of pembrolizumab every three weeks up to a total of 4 doses. This regimen was then immediately followed by a 200 mg dose of pembrolizumab alone every three weeks for no more than 2 years. Efficacy measures – response rates – and safety and tolerability parameters were then measured during a mean follow-up period of 12 months.

Participants enrolled in the study were all adults (median 64 years), and each participant had metastatic melanoma or unresectable disease with known BRAF mutations. Patients with uveal melanoma were excluded from this study. 

Findings from the study showed an overall response rate of 29% (20 participants), more than a doubling of the historical precedent for ipilimumab monotherapy of 13%. The median duration of response in these participants was 16.6 months. 

“We observed a significant level of antitumor activity with this therapeutic approach, and safety and tolerability were well within the range of acceptability. Adverse events of grade 3-4 levels occurred in 27% of our patients, and we experienced no mortalities as a result of the therapeutic approach,” says Dr. Luke. “The strong results from this study should be sufficient to begin larger randomized studies to learn more and confirm our initial findings.”

References and Further Reading

1. Olson DJ, Eroglu Z, Brockstein B, Poklepovic AS, Bajaj M, Babu S, Hallmeyer S, Velasco M, Lutzky J, Higgs E, Bao R, Carll TC, Labadie B, Krausz T, Zha Y, Karrison T, Sondak VK, Gajewski TF, Khushalani NI, Luke JJ.Pembrolizumab Plus Ipilimumab Following Anti-PD-1/L1 Failure in Melanoma. J Clin Oncol. 2021 Aug 20; 39(24): 2647-2655.

2. Huppert LA, Daud AI. Pembrolizumab and Ipilimumab as Second-Line Therapy for Advanced Melanoma. J Clin Oncol. 39(24): 2637-2638. Editorial.

Learn More About Dr. Luke and the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center.