A randomized double-blind trial of TQB2450 with or without anlotinib in pretreated driver-negative non-small cell lung cancer.

• Anlotinib, a novel antiangiogenic multikinase inhibitor, has been approved in China as third-line and above treatment for nonsmall cell lung cancer. • Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. • Anlotinib plus TQB2450 demonstrated promising antitumor activities in pretreated advanced NSCLC without EGFR and ALK alterations. • TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations. Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC. Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg. The primary outcome was progression-free survival (PFS) and the secondary outcomes included objective response rate (ORR). Thirty-three patients received TQB2450 plus placebo and 34 patients each received TQB2450 plus anlotinib 10 mg and 12 mg. At the data cutoff, the median PFS was 8.7 months (95% CI 6.1–17.1) in the TQB2450 plus anlotinib group and 2.8 months (95% CI 1.4–4.7) in the TQB2450 only group. The ORR reached 30.9% (95% CI 20.2%-43.3%) in the TQB2450 plus anlotinib group and was 3.0% (95% CI 0.1%-15.8%) in the TQB2450 only group. In patients with PD-L1 ≥ 1%, the ORR was 50.0% (95% CI 33.4%-66.6%) for TQB2450 plus anlotinib and 5.3% (95% CI 0.1%-26.0%) for TQB2450 plus placebo. No new safety signals were observed. Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. The study findings support the continued development of TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations. [ABSTRACT FROM AUTHOR]