Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial

• Published in: Journal of clinical oncology Vol. 41; no. 15; pp. 2724 - 2735
• Main Authors: Ascierto, Paolo Antonio, Lipson, Evan J, Dummer, Reinhard, Larkin, James, Long, Georgina V, Sanborn, Rachel E, Chiarion-Sileni, Vanna, Dréno, Brigitte, Dalle, Stéphane, Schadendorf, Dirk, Callahan, Margaret K, Nyakas, Marta, Atkinson, Victoria, Gomez-Roca, Carlos Alberto, Yamazaki, Naoya, Tawbi, Hussein A, Sarkis, Naomey, Warad, Deepti, Dolfi, Sonia, Mitra, Priyam, Suryawanshi, Satyendra, Grob, Jean-Jacques
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.05.2023; Wolters Kluwer Health
• Subjects: Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Humans; Life Sciences; Melanoma; Nivolumab - adverse effects; ORIGINAL REPORTS
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.22.02072

Nivolumab and relatlimab activity in advanced melanoma with prior progression on anti-programmed death-1/programmed death ligand 1 (PD-(L)1)-containing regimens is under investigation. RELATIVITY-047 demonstrated significantly improved progression-free survival (PFS) for nivolumab and relatlimab over nivolumab in previously untreated advanced melanoma. The phase I/IIa, open-label RELATIVITY-020 trial part D assessed efficacy and safety of nivolumab and relatlimab in advanced melanoma with progression during, or within 3 months of, 1 (D1) or ≥ 1 (D2) anti-PD-(L)1-containing regimens. Safety was a primary end point. Objective response rate (coprimary end point) and PFS by blinded independent central review (BICR) were assessed. Five hundred eighteen patients (D1 = 354; D2 = 164) received nivolumab and relatlimab. Among evaluable patients, the objective response rate by BICR was 12.0% (95% CI, 8.8 to 15.8) in D1 (n = 351) and 9.2% (95% CI, 5.2 to 14.7) in D2 (n = 163). Responses appeared to be enriched among patients with tumors expressing programmed death ligand 1 or lymphocyte activation gene 3; however, responses were observed regardless of programmed death ligand 1 and lymphocyte activation gene 3 expression (1%). The median duration of response was not reached (95% CI, 12.9 to not reached) in D1 and 12.8 months (95% CI, 6.9 to 12.9) in D2. The median PFS by BICR was 2.1 months (95% CI, 1.9 to 3.5) in D1 and 3.2 months (95% CI, 1.9 to 3.6) in D2; the 6-month PFS rate was 29.1% (95% CI, 24.2 to 34.1) and 27.7% (95% CI, 20.5 to 35.4), respectively. The grade 3-4 treatment-related adverse event incidence was 15.0% in D1 and 12.8% in D2. One case of grade 3 myocarditis and no treatment-related deaths occurred across part D. Nivolumab and relatlimab had a manageable safety profile and demonstrated durable clinical activity in a proportion of patients with heavily pretreated advanced melanoma with prior progression on anti-PD-(L)1-containing regimens. [Media: see text].