The invited discussant of LEAP-004, Bartosz Chmielowski, MD, PhD, Associate Clinical Professor at the University of California Los Angeles Jonsson Comprehensive Cancer Center, commented: “The response rate of 21% was quite impressive for this patient population. Patients previously treated with an anti–PD-1/PD-L1 agent plus an anti–CTLA4 drug had an even higher response rate, 31%, but we must interpret this with caution, since there were only 29 patients in this population,” he added.
Bartosz Chmielowski, MD, PhD
The median overall survival of 13.9 months also impressed Dr. Chmielowski, who indicated this is about double that achieved with nivolumab or nivolumab plus ipilimumab in a similar patient population.1 “This makes this finding even more important, and it tells us this combination might be an option for patients whose disease progressed on anti–PD-1/PD-L1,” he added.
Building upon the success of immunotherapy in melanoma, many studies are now evaluating agents to be paired with checkpoint inhibitors. Those studies showing promise in patients with resistance include pembrolizumab combined with talimogene laherparepvec, SD-101, CMP-001, or pIL12; nivolumab combined with relatlimab, bempegaldesleukin (NKTR-214), or CB-839; and ipilimumab given with tilsotolimod (Toll-like receptor 9 agonist). “LEAP-004 is not the only one that is promising. We are waiting for larger trials,” he said.
Looking ahead, Dr. Chmielowski hopes the treatment of melanoma can become more individualized. “We can easily identify three populations of patients treated with anti–PD-1/PD-L1 therapy: those with primary resistance, those with secondary (acquired) resistance, and those with long-term benefit,” he noted. “It will be important to come up with personalized immunotherapy, so based on the mechanism of resistance in patient populations, we would be able to choose their subsequent treatments.”
DISCLOSURE: Dr. Chmielowski has reported personal financial interests with Bristol Myers Squibb, Iovance, Lilly, Biothera, HUYA, Regeneron, Sanofi Genzyme, Array, Janssen, Genentech, Novartis, Merck, Compugen, EMD Merck Serrono, Immunocore, Eisai, Deciphera, Ideaya, and Epizyme.
1. Regan MM, Werner L, Rao S, et al: Treatment-free survival: A novel outcome measure of the effects of immune checkpoint inhibition—A pooled analysis of patients with advanced melanoma. J Clin Oncol 37:3350-3358, 2019.
Checkpoint inhibitors can be lifesaving for many patients with advanced melanoma, but those who experience disease progression currently have few treatment options. The combination of a tyrosine kinase inhibitor and an anti–PD-1 agent may offer some hope in this setting, according to a study of...