Abstract PO3-06-07: Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial

Abstract Background: Antiangiogenic drugs have demonstrated synergistic effect with anti-PD-1 antibody in advanced triple negative breast cancer (TNBC). Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Preclinical studies showed that metronomic chemotherapy inhibited angiogenesis and enhanced the efficacy of immunotherapy in TNBC via modulation of the tumor immune microenvironment. We hereby conducted a single-arm, multicenter, phase II trial to investigate the efficacy and safety of sintilimab (anti-PD-1 antibody) plus anlotinib and metronomic chemotherapy as a potential novel therapeutic strategy in advanced TNBC and explore potential biomarkers. Methods: Forty-four cases were planning to be included in this trial. The eligible patients who had received no more than two lines of chemotherapy for metastatic disease were enrolled and received sintilimab (200 mg iv q3w) and anlotinib (12 mg po d1-14 q3w) plus capecitabine (500 mg po, tid) or vinorelbine (40 mg po, tiw) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR) and secondary endpoints are disease control rate (DCR), progression free survival (PFS), and overall survival (OS). The safety profile has also been assessed. Results: As of April 2023, a total of 44 patients were enrolled, and 42 patients were evaluable for efficacy. 3 patients (7.1%) achieved complete response (CR). 6 patients (14.3%) achieved partial response (PR). 25 patients (59.5%) achieved stable disease (SD).The ORR is 21.4% (95%CI 0.103-0.368) and DCR is 81.0% (95%CI 0.810-0.659). The median PFS was 5.06 months (95%CI 2.051-8.069). The most common grade 1 or 2 adverse events (AEs) include elevated thyroid stimulating hormone (52.38%, 22/42), elevated bilirubin (23.81%, 10/42), hand-foot syndrome (22.22%, 8/42), leukopenia (16.67%,7/42), nausea (14.29%, 6/42). Grade 3 AEs include elevated bilirubin (2.38%, 1/42), hypertension (2.38%, 1/42) and herpes zoster (2.38%, 1/42). No grade 4 or 5 AEs occurred. Conclusions: Our date showed that sintilimab in combination with anlotinib plus metronomic chemotherapy have shown favorable efficacy and acceptable safety profile in patients with advanced TNBC. Clinical trial information: ChiCTR2100044725 Citation Format: huihui Li, Dongdong Zhou, Zeshun Yv, Yuqian Liao, Jie Huang, Shujuan Sun, fangchao zheng, Baojiang Li, Shu Fang, Ling Qiang, Guohua Ren, Bing Bu, Pengfei Qiu, Xinzhao Wang, Chao Li, Fangli Cao, Qian Shao, Dali Han, Lihua Song, Baoxuan Zhang, Bingjie Fan, Liang Xu, Xuemei Xie, Xianguang Zhao, Lanping Liu, Wanlong Li, Zhenbo Wang, Changmin Liu, Hui Fu, Xiao Sun, Zhiqiang Shi, Fengxiang Li. Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-07.