[[alternative]]Long-term follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer

[[abstract]]Background: Biliary tract cancer (BTC) is a rare, heterogenous, and lethal group of cancers with limited treatment options. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Prior analysis of this phase I study found an objective response rate of 23.3% and a manageable safety profile in patients with pretreated BTC who received bintrafusp alfa 1200 mg. We present long-term follow-up safety and efficacy data for bintrafusp alfa in patients with pretreated BTC. Methods: In this expansion cohort of an ongoing phase I, open-label trial (NCT02699515), Asian patients with BTC for which first-line (1L) chemotherapy failed received bintrafusp alfa 1200 mg Q2W until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary objective was safety/tolerability; secondary objectives included investigator-assessed best overall response per RECIST 1.1. Results: As of 24 October 2019, 30 patients with pretreated BTC received bintrafusp alfa for a median duration of 8.9 (range, 2-140.1) weeks; median follow-up was 122 weeks, 8 patients were still alive and 3 remained on treatment. The overall safety profile remained consistent with the prior analysis; with no additional deaths or safety signals, and 2 new grade ≥3 TRAEs (grade 3 rash and grade 3 keratoacanthoma). The median overall survival (OS) was 12.7 months [95% CI, [6.7-15.8]; the 12- and 24-month OS rates were 52.0% and 27.7%, respectively. The median duration of response was 18 (range, 2.8-24+) months, with 3 ongoing responses (18+, 23.5+, and 24+ months) of 7 responders (42.8%); the proportion of ongoing responses at 12 and 18 months was 57.1% and 42.8%, respectively. Conclusions: After 28 months, bintrafusp alfa continues to demonstrate manageable safety with durable responses and long-term survival in Asian patients with pretreated BTC. Bintrafusp alfa is under further investigation as a 1L (NCT04066491) and 2L (NCT03833661) treatment option for patients with locally advanced/metastatic BTC