Abstract 662: Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: A phase II trial

Abstract Background: Advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies with poor prognoses and limited treatment options. This first-in-class phase II study evaluated the efficacy and safety of SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGF-β, combined with famitinib, a multi-targeted receptor tyrosine kinase inhibitor, in patients with advanced BTC or PDAC who failed previous standard treatment. Methods: In this open-label, single-arm trial (ChiCTR2000037927), patients with advanced BTC or PDAC who had failed at least one line of prior therapy received SHR-1701 (30 mg/kg IV Q3W) plus famitinib (20 mg PO daily). The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory biomarker analyses were performed using RNA sequencing, multiplex immunohistochemistry, and machine learning. Results: Among 51 patients (BTC, n=25; PDAC, n=20), the BTC cohort showed an ORR of 28% (including 2 complete responses [CRs]) and a DCR of 80%, with a median PFS of 5.1 months and a median OS of 16.0 months. In the PDAC cohort, the ORR was 15% (2 CRs), with a DCR of 60%, and the median PFS and OS were 2.1 and 5.3 months, respectively. Grade 3/4 treatment-related adverse events occurred in 29.4% of patients, with no grade 5 events reported. Primary tumor resection history, peripheral blood immunophenotype changes, and distinct immune-metabolic profiles were associated with treatment benefits, with the TGF-β trap function of SHR-1701 potentially sequestering TGFB1 that was elevated in responders. An immune/metabolism (I/M) score integrating six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing to identify patients most likely to benefit from this therapy regimen. Conclusions: SHR-1701 plus famitinib showed promising efficacy and manageable toxicity in advanced BTC and PDAC, providing proof-of-concept for targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously. The I/M score may help select patients most likely to benefit from this regimen. Citation Format: Lixia Yi, Zhiqiang Meng, Jing Xie. Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: A phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 662.