Abstract PS4-07-30: A Phase II Trial of Ivonescimab in Combination with Carboplatin and Docetaxel in Patients with Early Stage Triple Negative Breast Cancer (TNBC)

Abstract Background: Immune checkpoint inhibitor pembrolizumab in combination with chemotherapy has shown promising pathological complete response rate (pCR) in early stage TNBC and currently FDA approved for stage II-III TNBC. 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. Ivonescimab showed promising progression free survival (PFS) in combination with paclitaxel or nab-paclitaxel as first line therapy, including PD-L1 negative TNBC. This phase 2 trial is designed to evaluate the efficacy and safety of ivonescimab in combination with carboplatin and docetaxel in early stage TNBC. Methods: This is a single center phase II study in patients (pts) with newly diagnosed early stage TNBC. Pts will receive neoadjuvant ivonescimab at 20 mg/kg, carboplatin AUC6 and docetaxel 75 mg/m2 every 3 weeks for a total of 6 cycles followed by breast surgery. Key eligibility criteria include: female or male ≥18; ECOG 0-1; newly diagnosed high-risk early stage TNBC, defined by ER≤10%, PR≤10% and HER2 negative per ASCO/CAP guideline; clinically ≥ T1cN0, or any T, N1-2 ; plan to receive neoadjuvant chemotherapy and immunotherapy as standard-of-care treatment; willing to undergo tumor biopsy prior to planned neoadjuvant systemic therapy; willing to provide post-treatment residual tumor at time of surgery. The primary endpoint is pCR. The secondary endpoints are event free survival (EFS), overall survival (OS), patient’s quality of life (QOL) by EORTC QLQ-C30. Peripheral blood, tumor tissue and stool sample will be collected at baseline, cycle 4 day 1, time of surgery for exploratory analysis: peripheral blood immune profiling, tumor immune profiles, stool microbiomes associated with the efficacy of the combination therapy. Statistical Design: We hypothesize that the addition of ivonescimab will increase the pCR rate to 78%. We will test the null hypothesis H0: θ < 0.58 versus the alternative hypothesis H1: θ > 0.58. The decision rule is to reject the null hypothesis if the posterior probability that θ > 0.58 given the data is sufficiently high, i.e, reject H0 if P (θ > 0.58 | data) > 0.94. A non-informative Jeffreys prior distribution beta (0.5,0.5) is placed on the parameter θ. One interim analysis for futility is planned using the Bayesian predictive distribution. With a sample size of 34 patients with one interim analysis for futility, the power to detect an absolute increase in pCR of 20% is 0.80. If the true value of θ is 0.58, the one-sided type I error is 0.046. The trial is projected to start patient enrollment in July 2025. Clinical trial information: NCT07017673 Citation Format: Y. Yuan, M. Tighiouart, A. Tan, A. Giuliano, S. Karlan, M. Boyle, C. Dang, A. Chung, F. Amersi, P. McAndrew, M. El-Masry, S. Sikaria, D. Chan, S. Valdez, N. Tank, T. Shaw, T. Wang, S. Shiao, S. Merlo, M. Walker, D. Calhoun, G. Park, J. Shen, A. Polverini, A. Terando, D. Lin, Y. Choi, J. Bitar. A Phase II Trial of Ivonescimab in Combination with Carboplatin and Docetaxel in Patients with Early Stage Triple Negative Breast Cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-30.