Abstract PD7-08: Exploratory phase II trial of camrelizumab (an anti-PD-1 antibody) combined with apatinib (a VEGFR-2 inhibitor) and chemotherapy as a neoadjuvant therapy for triple-negative breast cancer (NeoPanDa03): efficacy, safety and biomarker

Abstract Background: Chemotherapy serves as the primary therapeutic approach for triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. Methods: This study was a single-arm, open-label, single-center clinical trial (NCT05447702) involving patients with newly diagnosed stage II-III TNBC at West China Hospital. The treatment regimen consisted of camrelizumab (200 mg intravenously every 2 weeks, 12 cycles), apatinib (250 mg orally daily), and alternating chemotherapy [nab-paclitaxel (d1, 8, 15 every 4 weeks) for 4 cycles and epirubicin plus cyclophosphamide (every 2 weeks) for 4 cycles]. Results: From June 2023 to April 2024, 35 patients were enrolled, of whom 1 patient withdrew due to adverse reaction intolerance. At treatment completion, the total pathological complete response (tpCR, ypT0/is, ypN0) rate was 67.6% (23/34), and breast pCR (ypT0/is) rate was 70.6% (24/34). The overall response rate following neoadjuvant treatment reached 94.1% (32/34). Elevated levels of alanine aminotransferase (38.2%) and aspartate aminotransferase (29.4%) were the most common grade 3-4 adverse events, with no significant toxicities or treatment-related deaths reported. Genomic analysis revealed a significantly higher TP53 mutation rate in the pCR group (80% vs. 55.6%, P<0.05), while the non-pCR group exhibited a markedly elevated proportion of HRD-high patients (77.8% vs. 15.0%, P=0.01). Tumor microenvironment assessment confirmed reduced CD4+ T-cell infiltration (P=0.003) and enhanced fibroblast activation in non-pCR tumors. Comprehensive analysis of serum and tissue samples collected before and after neoadjuvant therapy via Olink and RNA sequencing revealed that the treatment induced a complex systemic immune response. These findings enabled the development of two novel scoring systems: a pretreatment response predictive score system for stratification and an efficacy assessment score system for treatment response evaluation. The PRPscore (baseline IL-18 + PD-L1 CPS) predicted pCR with an AUC of 0.823 (88% pCR rate in PRPscore-high group), while the EAscore (post-treatment IL-1α/IL-2/PTN/CXCL1/MMP7) evaluated therapeutic response with an AUC of 0.93 (exhibiting 100% non-pCR in EAscore-low group). The latter further implicated dysregulated IL-17 signaling as a potential therapeutic target. Conclusions: In conclusion, camrelizumab and apatinib combined with chemotherapy have good clinical efficacy and good safety as neoadjuvant treatments for stage II-III TNBC, warranting further investigation and potential clinical application. This innovative dual-score system stratifies pretreatment prognosis (PRPscore) and dynamically evaluates therapeutic efficacy (EAscore), enabling precision neoadjuvant optimization. Citation Format: T. Luo, Z. Chunying, X. Liu, D. Zheng, Y. Cheng, Y. Song, P. He, X. Yan, X. Zhong, T. Tian, B. Wei, Y. Xie, J. Chen, Q. Lv. Exploratory phase II trial of camrelizumab (an anti-PD-1 antibody) combined with apatinib (a VEGFR-2 inhibitor) and chemotherapy as a neoadjuvant therapy for triple-negative breast cancer (NeoPanDa03): efficacy, safety and biomarker analysis [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 PD7-08.