Immune checkpoint inhibitors targeting the programmed death receptor1 (PD1) and cytotoxic Tlymphocyte antigen 4 (CTLA4) pathways have provided significant clinical benefit for patients with unresectable or metastatic melanoma. However, a proportion of patients may not respond or may progress with current therapies. Lymphocyteactivation gene 3 (LAG3) is an additional immune checkpoint pathway that negatively regulates effector Tcell function and is a marker of Tcell exhaustion. Dual checkpoint inhibition of the LAG3 and PD1 pathways, by relatlimab and nivolumab, respectively, showed clinical activity in patients with previously treated metastatic or unresectable melanoma whose disease progressed during prior anti–PD(L)1 therapy, with a safety profile similar to nivolumab monotherapy (Ascierto P, et al. Presented at the ESMO 2017 Congress; September 8–12, 2017; Madrid, Spain. Oral LBA18). CA224047 will assess the clinical efficacy and safety of relatlimab in combination with nivolumab versus nivolumab alone in previously untreated metastatic or unresectable melanoma.
This is a randomized, multicenter, doubleblind, phase 2/3 study of relatlimab in combination with nivolumab versus nivolumab alone, in previously untreated metastatic or unresectable melanoma. Approximately 700 patients aged ≥12 years, with no prior systemic anticancer therapy for histologically confirmed stage III (unresectable) or stage IV (metastatic) melanoma and biopsy tissue available for biomarker analyses, are being randomized. Patients with active brain metastases or leptomeningeal metastases, or ocular melanoma are excluded. The primary endpoint for the phase 2 component is objective response rate, and for phase 3 is progressionfree survival. Other endpoints include overall survival, duration of response, disease control rate, and safety and tolerability. This study has started to enroll patients.
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Medical writing assistance was provided by Katerina Pipili, PhD, of Spark Medica Inc. (US), funded by Bristol-Myers Squibb.
E.J. Lipson: Research support: Bristol-Myers Squibb and Merck. Advisory board: Array BioPharma. G.V. Long: Consultancy services: Amgen, BMS, Merck MSD, Novartis, Roche, Pierre Fabre, Array. Honoraria: BMS, MSD, Roche, Novartis, Incyte. H. Tawbi: Research funding (institution): Merck, GlaxoSmithKline, Celgene; Research funding institution, Consulting fees: Bristol-Myers Squibb, Roche/Genentech. D. Schadendorf: Advisory board: BMS, Novartis, MSD, Sanofi, Regeneron, Incyte, Merck-Serono, Pfizer, Immunocore; Pierre Fabre, Roche; Corporate-sponsored research: BMS, Novartis. V.G. Atkinson: Advisory board: BMS, MSD, Novartis, Merck Serono, Pierre Fabre; Speakers fee: BMS, MSD, Roche, Novartis; Travel support: BMS, MSD. M. Maurer, K.L Simonsen, C. Harbison: Employee, Stock ownership: BMS. F.S. Hodi: Research support (institution): BMS; Consultant: BMS, Merck, Novartis, EMD Serono, Sanofi.