Phase 3 study of benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib for the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer (sq-NSCLC).

Abstract

8514 Background: PD-1/ PD-L1 inhibitors plus platinum-based chemotherapy is the standard first-line therapy for locally advanced or metastatic sq-NSCLC. Improvements in clinical benefits of sq-NSCLC receiving antiangiogenic agents and immune-checkpoint inhibitors have remained elusive, highlighting an urgent need to develop new therapeutic strategies. TQB2450-III-12 is a multicenter, randomized, double-blind, parallel-controlled phase III study of benmelstobart (PD-L1 inhibitor) in combination with chemotherapy followed by sequential combination with anlotinib (multi-targeted angiogenesis inhibitor) versus tislelizumab plus chemotherapy as first-line therapy for locally advanced or metastatic sq-NSCLC. Methods: Patients with unresectable locally advanced or metastatic sq-NSCLC without prior systematic therapy were randomized 1:1 to receive benmelstobart (1200 mg, Q3W) plus chemotherapy for 4 cycles followed with benmelstobart plus anlotinib (10mg, P.O., D1-D14, Q3W) (group A) or tislelizumab (200mg, Q3W) plus chemotherapy for 4 cycles followed with tislelizumab (group B). Paclitaxel (175 mg/m 2 , day 1) and carboplatin (area under the concentration [AUC] of 5, day 1) were given every 3 weeks. The primary endpoint was PFS per RECIST 1.1 by independent review committee and the key secondary endpoint was OS. Here we present the primary interim analysis for PFS per prespecified analysis plan. Results: As of March 1, 2024, 565 patients were randomized 1:1 to group A and group B. Baseline characteristics were well balanced. Median PFS was significantly improved in group A (10.12 months, 95% CI, 8.54–NE) versus group B (7.79 months, 95% CI, 6.87–9.69), HR=0.64 (98.35% CI, 0.45–0.93; P =0.0038). The subgroup analysis showed that PFS benefit favored group A in almost all subgroups, particularly in patients with ECOG PS 0 (HR 0.44, 0.23-0.84), PD-L1 expression (tumor proportion scoring) of 1-49% (HR 0.47, 0.30-0.73), and age <65 years (HR 0.59, 0.39-0.90). The ORR of group A and group B were 71.9% and 65.1%, respectively. The median DoR was longer in group A (9.69 months, 95% CI, 8.44, NE) than Group B (8.34 months; 95% CI, 5.78-NE) HR=0.58 (95% CI, 0.38, 0.88; P=0.0091). OS was immature. ≥Grade 3 benmelstobart/tislelizumab or anlotinib/ placebo-related adverse events was 61.57% in group A and 51.06% in group B. There was no difference of the grade 5 treatment-emergent adverse events (TEAE) between the treatment groups (group A: 5.69%, group B: 5.63%). The discontinuation of any treatment components by TEAE was 4.27% in group A and 5.28% in group B. Conclusions: Benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib significantly improved PFS, with a manageable safety profile. It might be a new first-line treatment for sq-NSCLC. Clinical trial information: NCT05718167 .