53O - Results from a phase II part I trial of mecbotamab vedotin (BA3011), a CAB-AXL-ADC, in patients with advanced refractory sarcoma

Background

AXL is a cell-surface receptor tyrosine kinase highly expressed in several sarcoma subtypes that has been associated with tumor resistance to chemotherapy. Mecbotamab vedotin (BA3011) is a conditionally active biologic anti-AXL antibody-drug conjugate (CAB-AXL-ADC) that conditionally and reversibly binds AXL under tumor-specific, low-pH conditions, which reduces off-tumor toxicity and immunogenicity, avoids tissue-mediated drug deposition, and improves pharmacokinetics.

Methods

This phase 2 part 1 open-label study evaluated BA3011 in adult and adolescent patients (pts) with AXL-expressing (tumor membrane percent score ≥50%) advanced refractory sarcoma who received either BA3011 monotherapy 1.8 mg/kg every 2 weeks (Q2W) or BA3011 1.8 mg/kg Q2W + nivolumab. Efficacy endpoints were disease control rate (DCR; objective response or stable disease for ≥12 weeks), number of responders (complete or partial), and progression-free survival (PFS) rate at week 12, while safety was assessed via treatment-emergent adverse events (TEAEs).

Results

Eighty-seven pts received BA3011 monotherapy and 26 received BA3011 + nivolumab. The median (range) duration of BA3011 treatment was 56.0 (11-315) and 56.5 (9-476) days in the monotherapy and combination therapy cohorts, respectively. The most common TEAEs of special interest among monotherapy pts were peripheral neuropathy (32.2%), neutropenia (25.3%), and abnormal liver function tests (20.7%). Grade 3+ TEAEs occurring in ≥5% of monotherapy pts included neutropenia (18.4%), decreased lymphocyte count (9.2%), and abdominal pain (5.7%). BA3011, with or without nivolumab, achieved a PFS rate of 39.9% and DCR of 41.1%, and 5 pts responded (Table).

Table: 53O

Efficacy of BA3011 monotherapy and BA3011 + nivolumab in patients with advanced refractory sarcoma

*One patient lost to follow-up was not evaluable for response rate and DCR. Abbreviations: CR, complete response; DCR, disease control rate; PFS, progression-free survival; PR, partial response.

Conclusions

Promising disease control with acceptable tolerability justifies further evaluation of BA3011 ± nivolumab in a randomized controlled trial among pts with heavily pretreated metastatic bone and soft tissue sarcomas.

Clinical trial identification

NCT03425279; EudraCT 2022-001111-10.

Editorial acknowledgement

Alec Jacobson, MD (MedLogix Communications, LLC).

Legal entity responsible for the study

BioAtla, Inc.

Funding

BioAtla, Inc.

Disclosure

S. Pollack: Financial Interests, Personal, Other, Advisory and consulting fees: Adaptimmune, Bayer, Boehringer Ingelheim, Deciphera, Rain Therapeutics, SpringWorks. A.P. Conley: Financial Interests, Personal, Funding, Research: Chordoma Foundation, Eli Lilly, EpicentRx, Inhbrx, Kronos, NCI, Roche; Financial Interests, Personal, Other, Consulting: Aadi Biosciences, Deciphera. W.D. Tap: Financial Interests, Personal, Funding, Research: BioAtla; Financial Interests, Personal, Advisory Board: Bayer, C4 Therapeutics, Certis Oncology Solutions, Daiichi Sankyo, Deciphera, Eli Lilly, Epizyme, MedPacto; Financial Interests, Personal, Other, Consulting: Abbisko, Adcendo, Amgen, Ayala Pharmaceuticals, Boehringer Ingelheim, BioAtla, C4 Therapeutics, Cogent Biosciences, Curadev, Daiichi Sankyo, Eli Lilly, Foghorn Therapeutics, Inhibrx, Innova Therapeutics, Ipsen, Kowa, Nuvation Bio, Osteosarcoma Institute, PharmaEssentia, Servier, Sonata; Financial Interests, Personal, Other, Travel expenses: Eli Lilly; Financial Interests, Personal, Stocks/Shares: Atropos Therapeutics, Certis Oncology Solutions; Financial Interests, Personal, Leadership Role, Co-founder: Atropos Therapeutics. C. Yen: Financial Interests, Personal, Funding, Research: BioAtla, Boehringer Ingelheim, Cogent Biosciences, Deciphera, Napo Pharmaceuticals, Ono Pharmaceutical, PharmaEssentia, Rain Therapeutics, Taiho, TDW Pharmaceuticals; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, CStone Pharmaceuticals, Daiichi Sankyo, Novartis, TDW Pharmaceuticals, TTY, ZiaLab. J. Charlson: Financial Interests, Personal, Advisory Role: Adaptimmune, Deciphera; Financial Interests, Personal, Other, Consulting: Adaptimmune, Deciphera. L. Davis: Financial Interests, Personal, Funding, Research: Adaptimmune, BioAtla, BTG, Epizyme, GSK, Inhbrx, Novartis, Salarius, SpringWorks; Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Inhbrx, Regeneron, SpringWorks. A. Chalmers: Financial Interests, Personal, Other, Research support: BioAtla, Boehringer Ingelheim, GSK, Tracon; Financial Interests, Personal, Other, Consulting: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: SpringWorks. M. Druta: Financial Interests, Personal, Advisory Role: Aadi Biosciences, AdaptImmune, Deciphera; Financial Interests, Personal, Other, Consulting: Aadi, AdaptImmune, Deciphera. E. Loggers: Financial Interests, Institutional, Funding, Research: Abbisko, Ayala Pharmaceuticals, BioAtla, Cogent, Dicephera, SpringWorks. G. Falchook: Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Advisory Role: AbbVie, BostonGene, BridgeBio, Fujifilm, Inspirna, Jubilant, Merck, Navire, Predicine, Regeneron, Sanofi, Silicon, Teon, Turning Point; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Other, Speakers' honorarium: CME from Rocky Mountain Oncology Society and Total Health Conferencing; Financial Interests, Personal, Other, Travel fees: Amgen, Bristol Myers Squibb, EMD Serono, Fujifilm, Millennium, Sarah Cannon Research Institute, Synthorx/Sanofi; Financial Interests, Institutional, Funding, Research: 3-V Biosciences, Abbisko, AbbVie, ABL Bio, Accutar, ADC Therapeutics, Agenus, Aileron, American Society of Clinical Oncology, Amgen, ARMO/Eli Lilly, Artios, AstraZeneca, Bayer, BeiGene, Bicycle, BioAtla, BioInvent, Bio-Thera, Black Diamond, Boehringer Ingelheim, Celgene, Celldex, Ciclomed, Curegenix, Curis, Cyteir, Daiichi Sankyo, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GSK, Hutchison MediPharma, IGM Biosciences, Ignyta, Immunitas, ImmunoGen/MacroGenics, Incyte, Jacobio, Jazz, Jounce, Jubilant, Kineta, Kolltan, Loxo/Bayer, MedImmune, Merck, Metabomed, Millennium, Mirati, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire/BridgeBio, NGM Bio, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, Pyxis, RasCal, Regeneron, Relay, Rgenix, Ribon, Roche, Samumed, Sapience, Seagen, Silicon, Simcha, Sirnaomics, Strategia, Syndax, Synthorx/Sanofi, Taiho, Takeda, Tallac, Tarus, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, University of Texas MD Anderson Cancer Center, Vegenics, Xencor, Zhuhai Yufan. T. Yau: Financial Interests, Personal, Advisory Role, Honoraria and Consulting: AstraZeneca, Bristol Myers Squibb, MSD, Exelixis, Ipsen, Eisai, Bayer, Novartis, EMD Sereon, AbbVie, Pfizer, Ei Lilly, Sirtex, Sillajen, Taiho, OrigiMed, New B Innovation, Sirtex, H3 Biomedicine. H.H.F. Loong: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, George Clinical, Illumina, Janssen, Merck Serono, Novartis, Takeda; Financial Interests, Personal, Speaker’s Bureau: Bayer, Eisai, Eli Lilly, Guardant Health, Novartis; Financial Interests, Institutional, Funding, Research: MSD, Mundipharma, Novartis. S. George: Financial Interests, Institutional, Funding, Research: BioAtla, Daiichi Sankyo, Deciphera, Eisai, IDRx, Merck, NewBay, Theseus, TRACON; Financial Interests, Personal, Advisory Board: Kayothera; Financial Interests, Personal, Other, Consulting: BioAtla, Blueprint, Deciphera, IDRx, Immunicum, NewBay; Financial Interests, Personal, Stocks/Shares: Abbott Labs, Pfizer. L. Mascarenhas: Financial Interests, Personal, Funding, Research: Amgen, AstraZeneca/MedImmune, Bayer, E.R. Squibb & Sons, Incyte, Jazz, Eli Lilly, Merck, Pfizer, Salarius, Turning Point; Financial Interests, Personal, Advisory Role: Gilead, Novartis. G.M. Cote: Financial Interests, Personal, Other, Honorarium: BioAtla, Gilead; Financial Interests, Personal, Other, Consultant: Chordoma Foundation, Sonata; Financial Interests, Personal, Advisory Board: C4 Therapeutics, Daiichi Sankyo, Eisai, Foghorn Therapeutics, Ikena Oncology; Financial Interests, Personal, Funding, Research: Bavarian Nordic, BioAtla, C4 Therapeutics, Eisai, Foghorn Therapeutics, Ikena Oncology, Inhibrx, Jazz, Kronos, MacroGenics, Merck KGaA/EMD Serono Research and Development Institute, PharmaMar, Pyxis, Rain Oncology, Repare Therapeutics, Servier, SMP Oncology, SpringWorks. B. Wilky: Financial Interests, Personal, Advisory Board: AADi, Adcendo, Boehringer Ingelheim, Deciphera, Epizyme, Polaris, Springworks; Financial Interests, Personal, Funding, Research Funding: Exelixis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Agenus Bio. All other authors have declared no conflicts of interest.