Phase II study of SHR-1701 combined with famitinib in the treatment of advanced pancreatic cancer or biliary tract cancer.

Abstract

568 Background: Pancreatic cancer (PC) and biliary tract cancer (BTC) are highly malignant cancers with limited treatment (tx) options. SHR-1701 is a novel bifunctional anti-PD-L1/TGF-βRII agent. Famitinib is a multitargeted tyrosine kinase inhibitor (TKI). Many studies have proved the mutually enhanced effect of anti-angiogenesis and ICI therapy in multiple tumours. Herein, we reported the safety and efficacy of SHR-1701 in combination with famitinib in advanced PC and BTC patients (pts) who have failed previous standard tx. Methods: This is an ongoing single-site, exploratory phase II study. PC or BTC pts who have failed ≥1 prior therapy would be enrolled into PC or BTC cohort, and received SHR-1701 plus famitinib until disease progression or unacceptable toxicity. SHR1701 would be intravenously given at a fixed dose of 30mg/kg q3w. Famitinib was initially given at a dose of 20mg/d. Dose reduction of famitinib to 15mg was allowed if it was intolerable. The primary endpoint was objective response rate (ORR) as per RECIST v1.1. Simon’s two-stage minimax design was used in this trial. For each cohort, if ≥2 responses are observed among 15 patients in stage I, the study will proceed to full accrual. Results: Up to 15 Sep 2021, 15 pts and 9 pts were enrolled in PC and BTC cohorts respectively. The baseline data are shown in the table. Of 15 evaluable pts in PC cohort, one had complete response, one had partial response (PR), 6 pts had stable disease (SD). The ORR and DCR were 13% and 53%, respectively. The first stage of PC cohort had a sufficient response rate to meet full enrollment. Among 8 evaluable pts in BTC cohort, one had PR (tumor shrinkage > 80%), 4 had SD. The ORR and DCR were 13% and 63%, respectively. 22 pts (92%) experienced treatment-related adverse events (TRAEs). The most frequently reported TRAEs (any grade) were proteinuria (58%), hypertension (42%), and blood urine present (42%). The incidence of Grade 3 TRAEs was 33%, among which the most common ones were hypertension (8%), and bilirubin conjugated increased (8%). No grade 4/5 TRAEs were reported. Conclusions: SHR-1701 plus famitinib showed encouraging activity with manageable safety in pts with advanced PC or BTC. Enrollment is ongoing and updated data will be presented. Clinical trial information: ChiCTR2000037927.[Table: see text]