Abstract 83TiP
Background
Mecbotamab vedotin (BA3011) is a conditionally active biologic (CAB) anti-AXL antibody-drug conjugate being developed as an anticancer therapy for patients with advanced solid tumors. Conditional and reversible binding by CABs is designed to reduce off-tumor toxicity and immunogenicity, avoid tissue-mediated drug disposition, and improve pharmacokinetics. AXL is a cell-surface transmembrane receptor protein tyrosine kinase highly expressed in several tumor types including sarcoma. Increased AXL expression has been associated with tumor resistance to chemotherapy, programmed death-1 (PD-1) inhibitors, molecular targeted therapy, and radiation therapy. The upregulation of AXL in PD-1 resistant tumor strongly suggests its role in resistance and recurrence in this population. Additionally, as patients who have experienced failure of either an epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor have been shown to achieve minimal benefit with subsequent exposure to PD-1 monotherapy, there is considerable additional rationale for use of BA3011-based therapy.
Trial design
Study BA3011-002 is an ongoing multi-center, open-label, phase II trial designed to evaluate the efficacy and safety of BA3011 alone or in combination with nivolumab in patients with AXL-expressing (tumor membrane percent score ≥ 1%), metastatic NSCLC who have measurable disease by RECIST version 1.1 criteria. To enroll, patients must have experienced failure of an approved programmed death1/ligand-1(PD-1/L1) treatment, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor (either monotherapy or in combination with another therapy such as ipilimumab). Treatment failure is defined as disease progression on a PD-1/L1, EGFR, or ALK inhibitor, or discontinuation of a PD-1/L1, EGFR, or ALK inhibitor due to an adverse event. Enrollment completion is anticipated in 2023.
Clinical trial identification
NCT04681131, EudraCT 2022-000135-23.
Legal entity responsible for the study
BioAtla, Inc.
Funding
BioAtla, Inc.
Disclosure
G. Dy: Financial Interests, Personal, Other, Consulting/honoraria: Amgen, AstraZeneca, Eli Lilly, Mirati, Regeneron, Takeda; Financial Interests, Personal, Principal Investigator: BioAtla. M. Alexander: Financial Interests, Personal, Principal Investigator: BioAtla. D.R. Camidge: Financial Interests, Personal, Advisory Role, Scientific Review Committee: Appolomics; Financial Interests, Personal, Advisory Role, ILD Adjudication Committee: AstraZeneca/Daiichi Sankyo, Mersana; Financial Interests, Personal, Advisory Role, DSMB: BeiGene; Financial Interests, Personal, Other, Consultancy: EMD Serono, Medtronic, Mirati, Onkure, Roche; Financial Interests, Personal, Principal Investigator: AbbVie, Pfizer, Dizal, Verastem, Karyopharm, Turning Point Therapeutics, Promontory Therapeutics, BioAtla.