R-ALPS: A randomized, double-blind, placebo-controlled, multicenter phase III clinical trial of TQB2450 with or without anlotinib as maintenance treatment in patients with locally advanced and unresectable (stage III) NSCLC without progression following concurrent or sequential chemoradiotherapy.

Abstract

LBA8004 Background: Benmelstobart (TQB2450) is a novel humanized IgG1 monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib, a multi-target antiangiogenic TKI, synergizes with PD-(L)1 inhibitors by normalizing tumor vasculature to enhance T-cell infiltration and augmenting antitumor immunity in advanced NSCLC. Methods: The phase III R-ALPS trial (NCT04325763) randomized 553 patients with locally advanced, unresectable stage III NSCLC and non-progression after concurrent/cequential chemoradiotherapy (60 Gy ± 10%) to three arms: 1) benmelstobart (1200 mg IV q3w) + anlotinib (8 mg po d1-14/q3w); 2) benmelstobart monotherapy; 3) placebo. Sample size: Phase I 1:1:1; Phase II 1:1. Stratification factors: Smoking:Yes/No; Prior treatment: Sequential/Concurrent. Primary endpoint: IRC-assessed PFS (RECIST 1.1). Results: At data cutoff (November 30, 2023): IRC-assessed mPFS: Combination arm: 15.15 months (95% CI 9.40-21.65) vs 4.17 months with placebo (HR 0.49 (95% CI 0.36-0.66), Log-rank p<0.0001; Monotherapy: 9.69 months (95% CI 5.98-34.43) vs 4.17 months with placebo (HR 0.53, 95% CI 0.39-0.72),Log-rank p<0.0001; 12-month PFS rates: 54.9% (combination) vs 45.7% (monotherapy) vs 26.4% (placebo). OS: OS data has not reached median time, pending updates. Grade ≥ 3 TEAEs: 8% (combination) vs 31.8% (monotherapy) vs 21.2% (placebo). Most frequent: Hypertension (8.6% vs 1.0% vs 1.5%), hypertriglyceridemia (9.6% vs 2.8% vs 1.5%). Treatment discontinuation due to TEAEs: 5% (combination) vs 14.2% (monotherapy) vs 9.1% (placebo). Treatment-related fatal due to TEAEs: 2%(combination) vs 1%(monotherapy) vs and 0.8%(placebo). At data cutoff (July 8,2024): IRC-assessed mPFS: Combination arm: 17.38 months (95% CI 12.45-24.77) vs 11.20 months (95% CI 7.00-20.73) with monotherapy (HR 0.82, 95% CI 0.63-1.08)，Log-rank p=0.1218. Conclusions: Benmelstobart, both as monotherapy and in combination with anlotinib, significantly prolonged PFS compared to placebo. Secondary endpoints also showed superiority, and the safety profile of the treatment group remained within acceptable parameters. (Funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; ClinicalTrials.gov number, NCT04325763). Clinical trial information: NCT04325763 .