A phase 1/2 dose-escalation and expansion study of a conditionally active anti-AXL humanized monoclonal antibody (BA3011) in patients with advanced solid tumors.

TPS12126 Background: The AXL receptor tyrosine kinase is often highly expressed in certain cancers. AXL appears to sustain resistance to anticancer therapies including chemotherapy, targeted therapy and immune checkpoint inhibitors (1, 2). BA3011 is an anti-AXL humanized monoclonal antibody conjugated to monomethyl auristatin E using a cleavable linker (CAB-AXL-ADC) and specifically binds to AXL under conditions found within the tumor microenvironment. The pharmacokinetic (PK) and toxicity profile of BA3011 has been established in cynomolgus monkeys; anti-tumor activity has been shown in non-small-cell lung cancer (NSCLC), pancreatic, castration-resistant prostate cancer (CRPC) and other tumor models. Methods: A multi-center, open-label, Phase 1/2 study will evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011 in patients with advanced solid tumors. The study consists of a dose-escalation phase (Phase 1) and a dose-expansion phase (Phase 2). The primary objective of Phase 1 is to define the safety profile (including dose-limiting toxicity [DLT]), maximum tolerated dose, and recommended Phase 2 dose (RP2D). BA3011 will be administered every 3 weeks (q3w) via intravenous infusion, with a starting dose of 0.3 mg/kg, escalating to 2.4 mg/kg using a modified Fibonacci method, until DLT occurs. In Phase 2, patients will receive the RP2D. Treatment will continue q3w until disease progression or unacceptable toxicity; safety and efficacy will be evaluated in specific tumor types (NSCLC, CRPC, and pancreatic ductal adenocarcinoma). Approximately 120 patients will be enrolled (11-30 in Phase 1 and approximately 90 in Phase 2). Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumors and have failed available standard-of-care therapy and for whom no curative therapy is available. Follow-up information will be collected approximately every 3 months after the last dose until disease progression for patients with stable disease or better at the end of treatment. Clinical trial information: NCT 03425279.