Abstract PO2-06-09: A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC)

Abstract Background: PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. Antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs). AK105, an anti-PD-1 antibody, can effectively prevents PD-1 from binding to PD-L1 and PD-L2, and avoid immune evasion of tumor cells. Anlotinib is a novel antiangiogenic, multi-target tyrosine kinase inhibitor which inhibits VEGFR, FGFR, PDGFR, c-KIT, c-RET and MET. This investigator initiated trial (IIT) (NCT05244993) aims to investigate the efficacy and safety of AK105, anlotinib combined with nab-P as a first-line therapy in pts with advanced TNBC. Methods: In this multicenter, prospective, single arm, phase 2 study, eligible pts were female aged 18-75 years, with ECOG PS 0-1, who had locally advanced or recurrent/metastatic triple-negative (estrogen receptor-, progesterone receptor- and HER2-) breast cancer. Eligible pts were treated with intravenous AK105 (200 mg on day 1), oral anlotinib (12 mg once daily on days 1-14) and intravenous nab-P (125 mg/m2 on days 1 and 8) . The triplet combination regimen repeated every 21 days until disease progression, death or intolerable toxicity. The primary endpoint is overall response rate (ORR), and the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS)and safety. Results: From July 2022 to July 2023, 19 patients were enrolled in this study. Median follow-up was 6.18 months (95% CI 1.29-11.06). Of all the patients whose efficacy could be evaluated (16/19), no patient achieved complete response (CR); 9(56.25%), 6(37.5%) and 1(6.25%) patients got partial response (PR), stable disease (SD) and progression disease (PD), respectively. ORR was 56.25 % (95% CI 30.55-79.25) and DCR was 93.75% (95% CI 67.71-99.67). mPFS and OS have not reached. The most common adverse events (AEs) were grade 1 or 2. The grade 3 AEs were neutropenia (15.79%), Leukopenia (10.52%), elevated ALT (5.26%), elevated AST (5.26%) and hypercholesteremia (5.26%). There were one case of grade 4 neutropenia and one case of grade 4 hypertriglyceridemia. No treatment-related death was observed. Conclusion: The combination of AK105, anlotinib and nab-P showed better treatment response and tolerable toxicity in the treatment of first-line patients with TNBC. Further studies enrolling more patients are still needed. Citation Format: Liang Zhang, Tao Sun. A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC) 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 PO2-06-09.