Phase 1/1b AB801 AXL receptor tyrosine kinase inhibitor with chemo + PD-(L)1 blockade

This Phase 1/1b, open-label, multi-cohort study evaluates AB801—an oral small-molecule AXL receptor tyrosine kinase inhibitor from Arcus Biosciences—combined with standard chemotherapy and immune checkpoint blockade in previously untreated cholangiocarcinoma or pancreatic ductal adenocarcinoma (PDAC). In the cholangiocarcinoma cohort, AB801 is given with gemcitabine (antimetabolite inhibiting DNA synthesis), cisplatin (DNA crosslinking platinum), and AstraZeneca’s durvalumab (PD-L1 monoclonal antibody). In the PDAC cohort, AB801 is combined with Gilead’s zimberelimab (PD-1 monoclonal antibody) plus FOLFIRINOX: oxaliplatin (platinum), irinotecan (topoisomerase I inhibitor), leucovorin (5-FU modulator), and 5-fluorouracil (thymidylate synthase/DNA synthesis inhibitor). Eligible patients include borderline resectable, locally advanced, or metastatic disease with no prior systemic therapy. The angle is biology-driven resistance reversal: AXL signaling is linked to invasion, immune evasion, and treatment resistance, so the trial tests whether AXL blockade can deepen and prolong responses to front-line chemo ± immunotherapy beyond today’s care—gemcitabine/cisplatin plus durvalumab in advanced biliary tract cancer, and modified FOLFIRINOX or gemcitabine/nab-paclitaxel in PDAC, where checkpoint inhibitors generally help only biomarker-selected subsets (for example MSI-high tumors).