Omid Hamid, MD

Omid Hamid, MD, Chief of Research/Immuno-Oncology, The Angeles Clinic & Research Institute, and Co-Director of the Cutaneous Malignancy Program at Cedars-Sinai Cancer Center, Los Angeles, commented on these two studies for The ASCO Post.

According to Dr. Hamid, the findings for the tumor lysate, particle-loaded, dendritic cell vaccine were “interesting and hypothesis-generating,” although he noted the trial had several confounding factors, including the use of a checkpoint inhibitor. “Many current trials are utilizing this approach to show benefit and are randomized between vaccine/checkpoint vs checkpoint alone. This is a cleaner approach since checkpoint inhibition is now standard in adjuvant and metastatic settings,” he commented.

Dr. Hamid mentioned two of these newer trials, which he believes “take a more personalized vaccine approach.” A current metastatic melanoma trial is using the personalized cancer vaccine RO7198457 in unresectable and metastatic melanoma, and KEYNOTE-942 is focusing on the adjuvant setting. The studies are evaluating the vaccine with and without pembrolizumab. “Given the lack of extra toxicity, this prime/boost approach may be the answer to a more active approach without risk,” Dr. Hamid proposed.

Triplet Therapy: ‘Ready to Come to the Fore’

Commenting on the COMBI-I trial, Dr. Hamid said triplet therapy in BRAF-mutated melanoma “is ready to come to the fore in care.” Initial trials such as KEYNOTE-022 and IMspire150 have shown a clear progression-free survival benefit in these patients, with information pending in relation to overall survival. Although toxicity is increased with three drugs, it is manageable, in his opinion.

“We have to see the true progression-free survival benefit and wait for overall survival data,” Dr. Hamid stated. “It is unclear how this regimen compares with dual immune checkpoint inhibition and what second-line options would be garnered after triplet therapy. The subset of patients receiving the least benefit with dual BRAF inhibition (more than three sites, high lactate dehydrogenase levels) need to be separately evaluated, as adding programmed cell death protein 1 inhibitors early may move the needle, given their poor prognosis. There is a trend in these studies toward higher complete response rates, and this may also be a positive predictor with immunotherapy in melanoma.” 

DISCLOSURE: Dr. Hamid has received honoraria from Array BioPharma, Bristol-Myers Squibb, Novartis, and Sanofi/Regeneron; has served as a consultant or advisor to Aduro, Akeso Biopharma, Amgen, Array BioPharma, BeiGene, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Immunocore, Incyte, Janssen, Merck, NextCure, Novartis, Regeneron, Roche, Sanofi, Seattle Genetics, Tempus, and Zelluna; has participated in a speakers bureau for Array BioPharma, Bristol-Myers Squibb, Novartis, and Sanofi/Regeneron; has received institutional research funding from Aduro Biotech, Akeso Biopharma, Amgen, Arcus Biosciences, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, CytomX Therapeutics, Exelixis, Genentech, GlaxoSmithKline, Immunocore, Incyte, Iovance Biotherapeutics, MedImmune, Merck, Merck Serono, Moderna Therapeutics, NextCure, Novartis, Pfizer, Regeneron, Roche, Sanofi, Seattle Genetics, Torque, and Zelluna.