CAMPASS: Benmelstobart in combination with anlotinib vs pembrolizumab in the first-line treatment of advanced non-small cell lung cancer (aNSCLC)—A randomized, single-blind, multicenter phase 3 study.

LBA8502 Background: Anti-PD-(L) 1 monotherapy has been the standard first-line treatment for PD-L1 positive NSCLC, but its clinical benefit remains unsatisfactory. Benmelstobart (TQB2450) is a humanized monoclonal antibody against PD-L1 and anlotinib is a multikinase inhibitor that has been approved as the standard of care in the third-line treatment of NSCLC in China. This phase 3 study aimed to compare the efficacy of benmelstobart in combination with anlotinib and pembrolizumab as first-line treatment of PD-L1 positive aNSCLC. Methods: This is a randomized, single-blind, multicenter phase Ⅲ study (NCT04964479). Eligible patients (pts) were previous systemic treatment naïve, diagnosed with locally advanced or recurrent/metastatic NSCLC and had PD-L1 positive expression (defined as TPS ≥1%). Pts were randomized in a 2:1 ratio to receive either benmelstobart plus anlotinib (benmel+ anlo) or pembrolizumab plus placebo (pem+placebo). Anlotinib or placebo was administered orally at a dose of 12/0mg QD on days 1-14 of a 21-day cycle, while benmelstobart or pembrolizumab was given intravenously at a dose of 1200mg or 200mg on the first day of each cycle. The primary endpoint was progression-free survival (PFS) assessed by independent review committee (IRC). Results: Between August 2021 and December 2022, 531 pts were randomized (528 treated). At the data cutoff date of 20 May 2023, the median follow-up for PFS was 11.4 months for the benmel+anlo arm and 10.6 months for the pem+placebo arm. The study met its primary endpoint that the median PFS was significantly prolonged to 11.0 months (95% CI 9.2-12.6) in the benmel+anlo arm compared with 7.1 months (95% CI 5.8-9.5) in the pem+placebo arm (P = 0.007). The hazard ratio (HR) was 0.70 (95% CI 0.55-0.91). The HR for pts with squamous cell carcinoma and PD-L1 expression ≥50% was 0.63 (95% CI 0.46-0.86) and 0.60 (95% CI 0.41-0.88). The confirmed objective response rate was also obviously higher with combination therapy (57.3% vs. 39.6%; P < 0.001). The data for overall survival (OS) was immature. In total, 98.3% of pts in the benmel + anlo arm and 88.1% in the pem + placebo arm experienced at least one treatment-related adverse event (TRAE). The incidence of grade ≥3 TRAE was 58.5% and 29.0% in each group, respectively. Only 5.7%/3.7% of pts permanently discontinued benmelstobart/anlotinib since TRAE, while termination of pembrolizumab/placebo due to TRAE occurred in 8.0%/2.3% of pts. Conclusions: To our knowledge, this is the first phase III study to demonstrate the significant PFS benefit of a multikinase inhibitor plus an anti-PD-L1 mAb in the first-line treatment of PD-L1-positive aNSCLC compared to pembrolizumab. Tolerability is favourable with a lower incidence of treatment discontinuation due to TRAE. The data support this combination as a new option for these pts. Clinical trial information: NCT04964479 .