First-line PD-1/VEGF bispecific antibody plus chemotherapy in triple-negative breast cancer: a phase 2 trial.

Abstract

Triple-negative breast cancer is an aggressive subtype comprising 10-20% of all breast cancer cases and has a worse prognosis than other subtypes. This open-label, multicenter, single-arm, phase 2 clinical trial evaluates the safety and efficacy of ivonescimab combined with chemotherapy as first-line treatment in female patients with locally advanced unresectable or metastatic triple-negative breast cancer who have not received previous systemic therapy. Eligible patients received ivonescimab 20 mg kg^-1 intravenously every 2 weeks and paclitaxel 90 mg m^-² or nab-paclitaxel 100 mg m^-² intravenously on days 1, 8 and 15 of each 4-week treatment cycle. The primary endpoints were safety and the investigator-assessed objective response rate per RECIST v.1.1. A total of 36 patients were enrolled. As of July 15, 2025, the median follow-up duration was 22.1 months. The primary endpoints were met. Treatment-related adverse events occurred in 36 (100.0%) patients. Grade ≥3 treatment-related adverse events were reported in 21 (58.3%) patients. No treatment-related deaths occurred. Immune-related adverse events occurred in 15 (41.7%) patients, with grade ≥3 events in 4 (11.1%) patients. Of the 35 patients evaluable for treatment efficacy, the objective response rate was 80.0% (95% confidence interval: 63.1-91.6), including 2 (5.7%) complete responses and 26 (74.3%) partial responses. Ivonescimab plus chemotherapy demonstrated encouraging antitumor activity as first-line therapy for patients with previously untreated advanced triple-negative breast cancer and merits further investigation. ClinicalTrials.gov identifier: NCT05227664 .