Ivonescimab is a humanized IgG1 bispecific anti-PD-1/VEGF antibody. This study aimed to evaluate the safety and tolerance of ivonescimab combined with etoposide and carboplatin as first-line treatment in patients with extensive-stage small cell lung cancer (ES-SCLC) and explore the primary efficacy of this regimen.Eligible patients received intravenous ivonescimab 3 mg/kg, 10 mg/kg, or 20 mg/kg every 3 weeks combined with etoposide and carboplatin for up to 4 cycles, followed by ivonescimab as maintenance. The primary endpoints were safety and objective response rate (ORR).Between April 23, 2021 and December 2, 2021, 35 patients were enrolled. At data cutoff (October 25, 2023), the median follow-up was 13.3 months (range, 0.3-28.5). For all patients, the confirmed ORR and disease control rate were 80% and 91.4%, respectively. The ORR was 66.7%, 90.9%, and 76.2% at the dose of 3 mg/kg, 10 mg/kg, and 20 mg/kg, respectively. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 21 patients (60%), and the most frequent toxicities were decreased neutrophil count (n=8, 22.9%), decreased white blood cell count (n=5, 14.3%), and anemia (n=5, 14.3%). Grade ≥3 TRAEs occurred in 66.7%, 54.5%, and 61.9% of patients in 3, 10, and 20 mg/kg groups, respectively. TRAEs leading to death were reported in 2 patients (5.7%). Adverse events with potential immunologic etiology, most of them grade 1 or 2, occurred in 14 patients (40.0%).Ivonescimab in combination with etoposide and carboplatin was well-tolerated and showed promising antitumor activity in ES-SCLC.Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.