444P - 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

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 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

43 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).

Results

As of April 2023, a total of 38 patients were enrolled, and 36 patients were evaluable for efficacy. 3 patients (8.3%) achieved complete response (CR). 6 patients (16.7%) achieved partial response (PR). 21 patients (58.3%) achieved stable disease (SD). The ORR is 25.0% (95%CI 0.12-0.42) and DCR is 83.3% (95%CI 0.67-0.94). The median PFS was 6.6 months (95%CI 2.12-11.08). The most common grade 1 or 2 adverse events (AEs) include elevated thyroid stimulating hormone (58.33%, 21/36), elevated bilirubin (27.78%, 10/36) , hand-foot syndrome (22.22%, 8/36), leukopenia (19.44%,7/36) and nausea (16.67%, 6/36) . Grade 3 AEs include elevated bilirubin (2.78%, 1/36), hypertension (2.78%, 1/36) and herpes zoster (2.78%, 1/36). 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 identification

ChiCTR2100044725.

Editorial acknowledgement

Legal entity responsible for the study

H. Li.

Funding

The Start-up fund of Shandong Cancer Hospital (Grant No.2020- PYB10) Beijing Science and Technology Innovation Fund (Grant No.KC2021-ZZ-0010-1) Natural Science Foundation of Shandong Province (No. ZR2022LZL004).

Disclosure

All authors have declared no conflicts of interest.