Multicenter phase 3 trial of benmelstobart with or without anlotinib after chemoradiotherapy for unresectable NSCLC

Consolidation immunotherapy improves outcomes after chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC). Disease progression remains common, and more effective consolidation strategies are needed. The double-blind phase 3 R-ALPS trial, at 42 centers in China, randomized patients without progression after CRT. In stage 1, patients were randomized 1:1:1 to two active regimens or placebp. In stage 2, additional patients were randomized 1:1 between the two active regimens. Patients were randomized to receive benmelstobart plus anlotinib, benmelstobart plus anlotinib placebo, or their matching placebos. Primary endpoint was the independent review committee (IRC)-assessed progression-free survival (PFS). Of 553 participants, 390 were randomized in stage 1, and 163 in stage 2. In stage 1, median PFS was 15.1 months with benmelstobart plus anlotinib, 9.7 months with benmelstobart alone, and 4.2 months with placebo. The HRs were 0.49 (95% CI 0.36-0.66) for benmelstobart plus anlotinib versus placebo and 0.53 (0.39-0.72) for benmelstobart versus placebo. In the pooled stage 1 and stage 2 analysis, median PFS was 17.4 months with benmelstobart plus anlotinib and 11.2 months with benmelstobart alone (HR 0,82; 95% CI0.63-1.08). Grade 3 to 5 treatment-related adverse events occurred in 48.8%, 29.4%, and 19.7% in the benmelstobart plus anlotinib, benmelstobart alone, and placebo groups, respectively; grade 5 events occurred in 7.2%, 1.4%, and 1.5%, respectively. The authors conclude that benmelstobart with or without anlotinib significantly improved PFS compared with placebo. Adding anlotinib did not significantly improve PFS compared with benmelstobart alone and incerased severe and fatal treatment-related adverse events.