Abstract 116TiP
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 deposition, and improve pharmacokinetics. AXL is a cell-surface transmembrane receptor protein tyrosine kinase highly expressed in several tumor types including sarcoma subtypes such as undifferentiated pleomorphic sarcoma (UPS). Increased AXL expression has been associated with tumor resistance to chemotherapy, programmed death-1 (PD-1) inhibitors, molecular targeted therapy, and radiation therapy.
Trial Design
Study BA3011-001 is an ongoing multi-center, open-label phase I/II first-in-human trial designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011 alone and in combination with the PD-1 inhibitor nivolumab in adult and adolescent patients 12 years and older with advanced solid tumors. Phase I comprises Dose Escalation and Dose Expansion and is designed to evaluate the safety and tolerability of BA3011 in adult patients with advanced solid tumors and to identify the BA3011 maximum tolerated dose and/or RP2D. Enrollment in phase I is completed. Phase II consists of 2 parts. Phase II part 1 is an open label study of BA3011 alone and in combination with nivolumab in adult and adolescent patients with high AXL-expressing tumor membrane percent score (TmPS) ≥ 50 with advanced refractory sarcoma. Enrollment is expected to be completed in 1H 2023. Phase II part 2 will enroll patients with locally advanced unresectable or metastatic UPS and high AXL expression (TmPS ≥ 50 ), randomized to receive open label BA3011 at two different dosing regimens. UPS patients may have received no more than 3 prior systemic regimens including investigational treatments but excluding treatment with PD-1/L1 inhibitor. Enrollment in phase II part 2 is expected to commence in January 2023.
Clinical trial identification
NCT03425279; EudraCT 2022-001111-10.
Editorial acknowledgement
Legal entity responsible for the study
BioAtla, Inc.
Funding
BioAtla, Inc.
Disclosure
B. Wilky: Financial Interests, Personal, Other, Consulting and Educational Program Development: Springworks; Financial Interests, Personal, Advisory Board: Deciphera, Adaptimmune, Daiichi Sankyo, Epizyme, Adcendo, Polaris; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Invited Speaker: Agenus Bio. J. Rodon: Financial Interests, Personal, Advisory Board: Peptomyc, Kelun Pharmaceuticals/Klus Pharma, Ellipses Pharma, Molecular Partners, iOnctura SA; Financial Interests, Institutional, Other, Clinical Research: Bayer, Novartis, Spectrum Pharmaceuticals, Symphogen, BioAlta, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline; Financial Interests, Institutional, Other, Research Funding: Blueprint Medicines, Black Diamond, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research Funding/Clinical Research: Hummingbird, Yingli; Financial Interests, Institutional, Research Grant, Research Funding: Vall d'Hebron Institute of Oncology/Cancer Core Europe; Financial Interests, Institutional, Research Grant, Clinical Research: Bicycle Therapeutics, Taiho, Roche Pharmaceuticals, Merus, Curis, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Hutchinson MediPharma, Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics; Other, Personal, Other, Other: VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, Boxer Capital, Llc, Tang Advisors, Llc; Other, Personal, Other, Travel Reimbursement: European Society for Medical Oncology. M. Ingham: Financial Interests, Personal, Advisory Role: Apexigen, Caris Life Sciences, Daiichi Sankyo, Epizyme, Xencor; Financial Interests, Personal, Research Grant: Apexigen, APICES, Mirati Therapeutics, PTC Therapeutics; Financial Interests, Personal, Other, Travel expenses: Genentech. S. Pollack: Financial Interests, Personal, Advisory Role: T-Knife, Epizyme, Aadi Bioscience, Obsidian, Bayer Corporation, Sensei, Springworks; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, Contractor: GlaxoSmithKline, SynOx, Springworks; Financial Interests, Personal, Research Grant: Obsidian; Financial Interests, Personal, Speaker’s Bureau: Deciphera. A.P. Conley: Financial Interests, Personal, Advisory Role: Bayer, Deciphera, Genentech, Guidepoint Global, InhibRx, Medscape, Nektar, Novartis, OncLive, Schlesinger Associates; Financial Interests, Personal, Research Grant: Bavarian Nordic, Ignyta, Iovance Biotherapeutics, Medimmune, NantHealth; Financial Interests, Personal, Other, Travel expenses: Genentech.