A phase II study to evaluate the safety and efficacy of anlotinib combined with penpulimab for advanced refractory biliary tract cancer.

Abstract

TPS582 Background: Although with modest efficacy, mFOLFOX is recommended as standard second-line chemotherapy for advanced biliary tract cancer (BTC). Several clinical trials are exploring the combination treatment of antiangiogenic drugs and immune checkpoint inhibitors. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor targeting VEGFR1/2/3, FGFR1-4 and PDGFRα/β, which effectively blocks tumor neovascularization and growth. Previous phase I/II clinical trials suggested that anlotinib combined with PD-(L)1 inhibitors as second-line therapy was well tolerated and showed clinical anti-tumor activity in advanced biliary tract cancer (NCT03825705, NCT03996408, ChiCTR1900022003, ChiCTR2000037847). Penpulimab is a novel humanized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect, and featuring slow antigen binding off-rate and high receptor occupancy. In this study, we explore anlotinib plus penpulimab as a chemo-free combination for second-line and above therapy. Methods: This is a prospective, single-arm, phase II study. BTC patients (pts) failed after the first-line treatment, aged 18-75 and an ECOG PS of 0-1 were recruited.Eligible pts received anlotinib (12mg, po, d1-14, q3w) and penpulimab (200mg, iv, d1, q3w) until disease progression, unacceptable toxicity or up to 2 years. The primary endpoint was Objective Response Rate (ORR). Secondary endpoints included Overall survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR) and safety. Based on a two-sided test for one proportion with 5.0% type I error, 80% power to detect an improvement in ORR from 5% to 22%, there will be 27 pts enrolled considering 20% of pts dropping out. Clinical trial information: ChiCTR2300069126 .