Safety and efficacy of bispecific antibodies in non-small cell lung cancer: A single-arm meta-analysis of randomized clinical trials.

440 Background: Bispecific antibodies represent a novel and promising class of therapeutics for solid tumors, including non-small cell lung cancer (NSCLC). Following the FDA approval of bispecific antibodies for NSCLC in 2024, interest in their clinical potential has grown substantially. This meta-analysis evaluates the safety and efficacy of bispecific antibodies in the treatment of NSCLC. Methods: A systematic search of PubMed/MEDLINE, CENTRAL, and ClinicalTrials.gov was conducted from inception through May 14, 2025, using predefined eligibility criteria. Randomized controlled trials (RCTs) assessing the efficacy and safety of bispecific antibodies in NSCLC were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes included safety profiles and detailed treatment response metrics. Statistical analyses were performed using R (version 4.5.0). Results: A total of 11 RCTs, involving 1224 patients, were included in the final quantitative synthesis. The pooled ORR was 26% (95% CI 0.13–0.45) and the DCR was 62% (95% CI 0.44–0.77). Rates of stable disease, partial response, and progressive disease were 31% (95% CI 0.24–0.39), 28% (95% CI 0.17–0.44), and 25% (95% CI 0.15–0.39), respectively. The overall incidence of any adverse event (AE) was 87% (95% CI 0.78-0.92), compared to much lower incidence of serious adverse events at 26% (95% CI 0.14-0.43). Immune-related AEs were observed in 49% (95% CI 0.40–0.57) patients. Treatment-related AEs (TRAEs) led to discontinuation in 8% of patients (95% CI 0.04–0.17), to drug interruption in 21% (95% CI 0.12–0.34), and to death in 2% (95% CI 0.01–0.04). Conclusions: Bispecific antibodies demonstrate promising efficacy with an acceptable safety profile in the treatment of NSCLC. While adverse events are common, the incidence of severe or treatment-limiting toxicity remains relatively low. Continued investigation through larger, long-term trials is warranted to validate their role in clinical practice.