Brief report: Ivonescimab combined with etoposide plus carboplatin as first-line treatment for extensive-stage small-cell lung cancer: results of a phase Ib clinical trial.

Introduction: 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.

Methods: 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).

Results: 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%).

Conclusions: Ivonescimab in combination with etoposide and carboplatin was well-tolerated and showed promising antitumor activity in ES-SCLC.