A randomized clinical trial of chemotherapy with gemcitabine/cisplatin/nabpaclitaxel with or without the AXL inhibitor bemcentinib (BGB324) for patients with advanced pancreatic cancer.

TPS473Background: The Axl pathway coordinately mediates immune evasion and drug resistance in pancreatic cancer. Systemic Axl inhibition can enhance the efficacy of cancer therapy by blocking tumor cell proliferation, survival and drug resistance associated with epithelial-mesenchymal transition (EMT), and targeting innate immune suppression in the tumor microenvironment. Bemcentinib (BGB324) is a first in class, selective oral inhibitor of Axl. Our group has shown that bemcentinib therapy, in combination with gemcitabine, improved survival in multiple preclinical models of pancreatic cancer. Methods: This is a multicenter, randomized, phase 1b/2 clinical trial of nab-paclitaxel/gemcitabine/cisplatin with or without bemcentinib. Patients with metastatic pancreatic cancer, good performance status and preserved liver, kidney and hematologic function are eligible. The treatment schedule is as follows: Bemcentinib 100 or 200 mg daily, nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 int...