Abstract PS3-05: Evaluation of the safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC)

Abstract Background: Locally advanced unresectable or metastatic TNBC is highly aggressive and has a poor prognosis. Ivonescimab, a tetravalent bispecific antibody targeting PD-1 and VEGF, has the potential to produce synergistic anti-tumor effects through both pathways via cooperative binding. This study aimed to evaluate the safety and efficacy of ivonescimab in combination with chemotherapy in locally advanced unresectable or metastatic TNBC. Methods: This was an open-label, multicenter phase II study in patients (pts) with locally advanced unresectable or metastatic TNBC. Pts received ivonescimab at 20 mg/kg Q2W and paclitaxel at 90 mg/m2 or nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th day of each four-week treatment cycle. The primary endpoints were safety and objective response rate (ORR) by RECIST1.1. The secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: As of May 31, 2024, a total of 30 pts with locally advanced unresectable or metastatic TNBC were enrolled. The median age was 54.0 years (range, 35.4-73.3), 53.3% of pts had ECOG of 1, 80% of pts had a PD-L1 combined positive score (CPS) <10, and 60% of pts had previously received taxane-based neoadjuvant or adjuvant therapy. The median follow-up was 10.12 months (range: 2.66+, 15.77). A total of 53.3% (16/30) of pts experienced at least one ≥Grade 3 treatment-related adverse event (TRAE), but none led to treatment discontinuation or deaths. The most common ≥Grade 3 TRAEs with a frequency ≥10% included neutrophil count decreased (16.7%) and white blood cell count decreased (16.7%). Twenty-nine pts had at least one post-baseline tumor assessment; the ORR by investigator assessment was 72.4% (21/29) and the DCR was 100% (29/29). The ORRs of PD-L1 CPS ≥10 and PD-L1 CPS <10 were 83.3% (5/6) and 69.6% (16/23), respectively. The median PFS was 9.3 month (95% CI: 6.24, NE), the 9-month PFS rate was 56.6% (95% CI: 32.2, 75.1). In the PD-L1 CPS ≥10 population, the median PFS was not reached (95% CI: 5.36, NE), the 9-month PFS rate was 60% (95% CI: 12.6, 88.2). In the PD-L1 CPS <10 population, the median PFS was 9.3 month (95% CI: 5.55, NE), the 9-month PFS rate was 52.6% (95% CI: 22.5, 75.8). The median DoR was 7.49 month (95% CI:3.91, NE). In the PD-L1 CPS ≥10 population, the median DoR was not reached (95% CI: 3.58, NE). In the PD-L1 CPS <10 population, the median DoR was 7.49 month (95% CI: 3.91, NE). The median OS was not yet mature. Conclusion: Ivonescimab in combination with chemotherapy showed promising anti-tumor activity and acceptable tolerable safety as 1L treatment of TNBC. Further trials to confirm the results are warranted. Citation Format: Xiaojia Wang, Quchang Ouyang, Can Tian, Xiying Shao, Jian Huang, Zhanhong Chen, Yongsheng Wang, Tao Sun, Tienan Yi, Xufang Yu, Zhongmin Wang, Baiyong Li, Michelle Xia. Evaluation of the safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-05.