Citations 1
Phase I/II Study of AXL-Specific Antibody–Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors
Rohrberg, Kristoffer Staal , Lopez, Juanita , Milhem, Mohammed , Blank, Christian U. , Reijers, Irene L. M. , Plummer, Ruth , Piha‐Paul, Sarina A. , Jänne, Pasi A. , Shaw, Heather M. , Debruyne, Philip R. , Lao, Cristopher , Gort, Eelke , Zhao, Yujie , Schöffski, Patrick , Chen, Andrew William , Cohen, Eric A. , Katz, Sharyn I. , Brady, Luther W. , Qutaish, Mohammed , Castro, Patricia Garrido , Pencheva, Nora , Fu, Yali , Windfeld, Kristian , Reiter, Panagiota , Amiri, Katayoun I. , Ahmadi, Tahamtan , Forssmann, Ulf , Vergote, Ignace , Lopez, Juanita S , Milhem, Mohammed M , Reijers, Irene , Thistlethwaite, Fiona , Plummer, Ruth , Piha-Paul, Sarina A , Jänne, Pasi A , Shum, Elaine , Shaw, Heather M , Debruyne, Philip R , Lao, Cristopher , Baurain, Jean-Francois , Choe, Jennifer H , Gort, Eelke , Zhao, Yujie , Jerusalem, Guy , Schöffski, Patrick , Chen, Andrew William , Cohen, Eric A , Mankowski, Walter C , Roshkovan, Leonid , Katz, Sharyn I , Kontos, Despina , Brady, Lauren K , Qutaish, Mohammed , Castro, Patricia Garrido , Pencheva, Nora , Bajaj, Gaurav , Fu, Yali , Windfeld, Kristian , Reiter, Panagiota , Jure-Kunkel, Maria , Higgs, Brandon W , Amiri, Katayoun I , Ahmadi, Tahamtan , Forssmann, Ulf , Ramalingam, Suresh S. , Vergote, Ignace , Baurain, Jean‐François , Jérusalem, Guy , Mankowski, Walter C.
Cancer Research Communications | October 30, 2025 | Volume: 5 | Issue: 11 | Pages: 2066-2078
Abstract Purpose: AXL, a receptor tyrosine kinase related to oncogenic processes, is aberrantly expressed in various cancers and associated with treatment resistance. Enapotamab vedotin (EnaV), a novel anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, demonstrated antitumor activity in preclinical models, including non–small cell lung cancer (NSCLC). This phase 1/2 study assessed the safety and preliminary efficacy of EnaV in solid tumors. Patients and Methods: This study comprised dose-escalation and dose-expansion phases; both phases investigated EnaV once every 3 weeks (Q3W) and EnaV on days 1, 8, and 15 of a 28-day cycle (3Q4W). Primary objectives determined the maximum tolerated dose (dose escalation) and safety (dose expansion). Pharmacokinetic profile, antitumor activity, and AXL expression were also assessed. Results: During dose escalation, 32 patients received EnaV Q3W; 15 received EnaV 3Q4W. The maximum tolerated dose and recommended phase 2 dose were 2.2 mg/kg in Q3W and 1.0 mg/kg in 3Q4W schedules. In dose expansion, 189 patients received EnaV Q3W; 70 received EnaV 3Q4W. Common adverse events in dose expansion included fatigue, constipation, nausea, decreased appetite, and diarrhea. Overall response rates ranged from 4.5% to 12.5% with Q3W dose schedule and from 9.1% to 11.5% with 3Q4W dose schedule. Disease control rates for NSCLC cohorts were 40.9% to 50.0%. NSCLC subset analysis demonstrated correlation between radiomics signature and disease control. The relationship between clinical activity and AXL expression was not apparent. Conclusions: EnaV had an acceptable safety profile; however, because the evaluation of antitumor activity did not show clinically meaningful responses, clinical development of EnaV was discontinued. Significance: EnaV, an anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, showed single-agent antitumor activity in preclinical models. This phase 1/2 study of EnaV demonstrated a manageable safety profile and antitumor activity in selected tumor types. Further studies exploring alternative targeting modalities, patient selection, and/or combinations are needed.