Abstract OT2-08-01: 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

Abstract Background: PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. As antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs), we designed an investigator initiated trial (IIT) to investigate the efficacy and safety of AK105 (anti-PD-1 antibody), anlotinib (antiangiogenic, multi-target tyrosine kinase inhibitor) combined with nab-P as a first-line therapy in pts with advanced TNBC. Method: 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. The main exclusive criteria were previous use of PD-1/PD-L1 antibody, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or antiangiogenic agent, and central nervous system (CNS) metastases. Eligible pts were treated with intravenous AK105(200mg on day 1), oral anlotinib(12mg once daily on days 1-14) and intravenous nab-P (125mg/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. Simon’s two-stage design were used to calculate the sample size assuming ORR is improved from 45.9% (nab-P alone) to 65% (AK105, anlotinib combined with nab-P) with the power (1-β) taken as 0.80 and the type I error (α) taken as 0.05 (two-sided). Enrollment began in June 2022 with a total goal of 42 pts at 7 sites in China. Clinical trial information: NCT05244993. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Citation Format: Tao Sun, Liang Zhang. 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 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-08-01.