Phase Ib Trial of Batiraxcept in Combination With Nab-Paclitaxel and Gemcitabine for Previously Untreated Advanced Pancreatic Cancer

PURPOSE Increased anexelekto (AXL) pathway signaling in pancreatic cancer can increase cellular invasion, migration, proliferation, and protumoral infiltration of tumor-associated macrophages and fibroblasts. Batiraxcept acts as a novel decoy immunoglobulin G1 heavy chain (Fc) fusion protein with high affinity to GAS6, the ligand for AXL receptor. METHODS This phase Ib trial evaluated batiraxcept at 15, 20, and 25 mg/kg intravenously on day 1 and 15 combined with nab-paclitaxel and gemcitabine in untreated locally advanced or metastatic pancreatic cancer. Primary end points were safety, recommended phase II dose, and objective response rate (ORR) using RECIST v1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), exposure-response relationships per pharmacokinetic data (PK), and pharmacodynamic effects on serum GAS6. RESULTS Twenty-eight patients (median age 67.5 years, 64% female, 75% non-Hispanic White) received batiraxcept at 15 mg/kg (n = 21) and 20 mg/kg (n = 7) in combination with nab-paclitaxel and gemcitabine. The ORR, median PFS, and median OS at 15 mg/kg dose were 29%, 5.4 months, and 10.7 months, respectively. Based upon exposure-response modeling, a minimum efficacious concentration (MEC) of 14.5 mg/L for batiraxcept was identified. The median PFS with >MEC and ≤MEC was 5.6 and 2.7 months, while the median OS was not reached and 8.3 months ( P = .03), respectively. Across both doses, 20 (71%) patients had batiraxcept-related adverse events, including infusion-related reactions (21%) and any grade ≥3 event in seven (25%), of which fatigue (14%), and neutropenia (11%) were most commonly reported. CONCLUSION Batiraxcept in combination with nab-paclitaxel and gemcitabine was well tolerated. Patients receiving 15 mg/kg with a PK trough >MEC had longer PFS and OS. Unfortunately, the study was terminated early because of dissolution of the pharmaceutical company.