First-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in Chinese patients with unresectable or metastatic melanoma: Results from LEAP-003.

9553 Background: Results of the global, phase 3 LEAP-003 study, showed that lenvatinib (len) + pembrolizumab (pembro) significantly improved PFS compared with pembro alone in participants (pts) with predominantly cutaneous melanoma at the first interim analysis, but this benefit was not maintained with additional follow-up and there was no improvement in OS. Previous studies have shown that mucosal and acral melanomas, which are the predominant subtypes in Chinese patients, may benefit from combination therapy. Here, we present results for Chinese participants (pts) enrolled in the LEAP-003 global (NCT03820986) and China extension (NCT04889118) studies. Methods: Eligible pts were aged ≥18 y, had previously untreated unresectable stage III or IV melanoma, an ECOG PS of 0 or 1, and measurable disease per RECIST v1.1. Pts were randomly assigned 1:1 to len 20 mg or placebo (pbo) PO QD + pembro 200 mg IV Q3W for ≤2 y. Dual primary end points were PFS per RECIST v1.1 by BICR and OS. Secondary end points were ORR, DOR, and safety. Results: 131 pts from China enrolled and received treatment (len + pembro, n = 64; pbo + pembro, n = 67). Median time from first dose to data cutoff (Jan 18, 2023) was 18.1 mo (range, 12.7-29.5). In the overall China subgroup, median PFS was 6.1 mo (95% CI, 4.1-8.1) for len + pembro vs 2.0 mo (95% CI, 2.0-2.1) for pbo + pembro (HR, 0.55; 95% CI, 0.37-0.81); 18-mo PFS was 20.0% vs 12.8%. Median OS was 19.9 mo (95% CI, 11.9-26.8) for len + pembro vs 17.0 mo (95% CI, 12.7-25.7) for pbo + pembro (HR, 0.93; 95% CI, 0.58-1.48); 18-mo OS was 53.4% vs 49.6%. ORR was 26.6% (95% CI, 16.3-39.1; 4 CR, 13 PR) for len + pembro vs 16.4% (95% CI, 8.5-27.5; 4 CR, 7 PR) for pbo + pembro; median DOR was 13.7 mo (range, 3.8-21.4) vs NR (range, 4.2-21.4+). Among 30 pts with mucosal melanoma, median PFS was 8.1 mo (95% CI, 5.9-12.4) for len + pembro (n = 16) vs 2.0 mo (95% CI, 1.9-4.1) for pbo + pembro (n = 14; HR, 0.44; 95% CI, 0.20-0.97); 12-mo PFS was 33.5% vs 21.4%. Median OS was 26.8 mo (95% CI, 10.6-NR) for len + pembro vs 14.3 mo (95% CI, 9.0-NR) for pbo + pembro (HR, 0.51; 95% CI, 0.17-1.55); 18-mo OS was 68.8% vs 49.0%. ORR among pts with mucosal melanoma was 50.0% (95% CI, 24.7-75.3; 1 CR, 7 PR) for len + pembro vs 7.1% (95% CI, 0.2-33.9; 1 PR) for pbo + pembro. Treatment-related AEs occurred in 96.9% in the len + pembro arm vs 97.0% in the pbo + pembro arm (grade 3-5: 62.5% vs 16.4%). One pt (1.5%) in the pbo + pembro arm died due to treatment-related immune-mediated lung disease. Conclusions: In Chinese pts, the efficacy and safety profile observed with len plus pembro vs pembro alone was consistent with the global population. Numerical improvements in PFS and ORR in the mucosal melanoma subtype treated with len + pembro were notable, although the data should be interpreted with caution due to the limited sample size. These results support first-line pembro monotherapy as a standard-of-care for this population. Clinical trial information: NCT03820986 , NCT04889118 .