Nivolumab plus relatlimab vs nivolumab alone for the adjuvant treatment of completely resected stage III–IV melanoma: Primary results from RELATIVITY-098.

Abstract

LBA9500 Background: NIVO + RELA fixed-dose combination (FDC), compared with NIVO alone, demonstrated a clinically meaningful benefit to progression-free survival (HR 0.79, 95% CI 0.66–0.95) and overall survival (OS; 0.80, 95% CI 0.66–0.99) after a 3-y follow-up, with a manageable safety profile in patients (pts) with untreated advanced melanoma (RELATIVITY-047). To address a current unmet need for more efficacious adjuvant regimens for completely resected melanoma, RELATIVITY-098 was designed to evaluate adjuvant NIVO + RELA FDC vs NIVO alone in pts after complete resection of stage III–IV melanoma (NCT05002569). Methods: In this phase 3, randomized, double-blind study, pts aged ≥ 12 years were stratified by AJCC v8 stage at screening (stage IIIA/IIIB vs IIIC vs IIID/IV) and geographic region (USA/Canada/Australia vs Europe vs rest of the world). Pts were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg FDC or NIVO 480 mg every 4 weeks for a maximum of 1 year or until first recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival (RFS) by investigator; secondary endpoints included OS (key), distant metastasis-free survival (DMFS), and safety. Results: Pts randomized to NIVO + RELA (n = 547) vs NIVO alone (n = 546) had stage IIIA/B (38% vs 36%) or IIIC (49% vs 50%) disease; 80% vs 83% had cutaneous nonacral melanoma, 11% vs 10% had cutaneous acral, and 2% vs 1% had mucosal. Median duration of therapy was 11.0 mo for each arm. At a minimum follow-up of 23.4 mo, there was no statistical difference in RFS for NIVO + RELA vs NIVO (Table). The RFS outcome was generally consistent across stratification factors and prespecified subgroups. OS was not tested per the hierarchical testing strategy. There were 148 OS events (48% data maturity). DMFS was similar in both treatment groups (Table). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 19% of pts treated with NIVO + RELA vs 8% with NIVO alone (compared with 22% vs 12% in RELATIVITY-047); any-grade TRAEs led to discontinuation of therapy in 17% vs 9% of pts, respectively. There were 2 treatment-related deaths with NIVO + RELA and 1 with NIVO. Conclusions: NIVO + RELA did not result in significant RFS improvement vs NIVO alone as adjuvant treatment for pts after complete resection of stage III–IV melanoma. The safety profile of NIVO + RELA in this setting was generally consistent with results from RELATIVITY-047. A robust biomarker analysis for the study is currently underway. Clinical trial information: NCT05002569 . NIVO + RELA NIVO RFS 24-mo rate, %(95% CI) 62.0(57.7–66.0) 63.6 (59.4–67.6) Median, mo (95% CI)(events/pts) NR (30.8–NR)(214/547) 33.1 (31.0–NR)(213/546) HR 1.01 (95% CI, 0.83–1.22) DMFS 24-mo rate, %(95% CI) 73.1(68.8–76.9) 76.3(72.3–79.9) Median, mo (95% CI)(events/pts) NR (NR–NR)(133/499) 33.1 (31.5–NR)(129/494) HR 1.07 (95% CI 0.84–1.36) HR, hazard ratio; NR, not reached.