Omid Hamid, MD
Omid Hamid, MD, Chief of Research/Immuno-Oncology at The Angeles Clinic & Research Institute and Co-Director of the Cutaneous Malignancy Program at Cedars-Sinai Cancer Center, Los Angeles, commented on the investigational use of bempegaldesleukin in melanoma.
“The role of interleukin-2 [Il-2] therapy has never been disputed and now continues to grow in malignant melanoma,” Dr. Hamid said. He explained that bempegaldesleukin (NKTR-214) is an engineered IL-2 cytokine prodrug that provides sustained activation of the IL-2 pathway with a bias to the IL-2 receptor CD122 (IL-2Rβ); this avoids off-target treatment-related toxicity. Its use leads to increases in tumor-infiltrating lymphocytes, depletion of regulatory T cells, and increases in T-cell clonality and PD-1 expression, along with the proliferation of CD8 effector cells and natural killer cells—“factors associated with response to immunotherapy.”
Preclinically, bempegaldesleukin in combination with anti–PD-1 therapy has resulted in a higher response rate, prolonged disease control, and more complete responses in a variety of preclinical tumor types (including colon cancer, melanoma, bladder cancer, lung cancer, and breast cancer).1
‘A Possible Success’
“Although the response rate seen in this phase II study [ClinicalTrials.gov identifier NCT03635983] is no different from similar combination trials that promised a new standard but fizzled in subsequent evaluations, the complete response rate of 34% far exceeds its predecessors. It is this that heralds it as a possible success,” Dr. Hamid pointed out.
“Patients with complete responses have the best progression-free and overall survival of any subgroup of patients treated with checkpoint therapy—either as single agents or in combination.1 This population remains in response after discontinuation of therapy,” he noted.
Dr. Hamid continued: “There is promise in a combination that boasts similar response rates (55%) with lower grade 3 or 4 toxicity (17%) and higher complete response rates! However, one must take a step back and realize these data are based on 38 patients. More data are yet to come.”
The combination of bempegaldesleukin and nivolumab is being evaluated in a randomized trial vs nivolumab alone in 784 patients. The promise of this approach has also bolstered the early evaluation of this combination in the adjuvant melanoma setting (NCT04410445). Furthermore, its lack of significant toxicity has led to triplet trials with bempegaldesleukin, anti–PD-1 agents, and CTLA-4 inhibitors or tyrosine kinase inhibitors, Dr. Hamid indicated.
Follow Dr. Hamid @OmidHamidMD.
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.
1. Robert C, Ribas A, Hamid O, et al: Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma. J Clin Oncol 36:1668-1674, 2017.
A first-line regimen combining the novel interleukin-2 (Il-2) agonist bempegaldesleukin (NKTR-214) with nivolumab showed encouraging clinical activity in patients with metastatic melanoma in the phase I/II PIVOT-02 trial, according to a presentation during the 2020 Annual Meeting of the Society for ...