{"@context":"https://schema.org","@type":"ScholarlyArticle","headline":"Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors.","author":[{"@type":"Person","name":"Kristoffer Staal Rohrberg"},{"@type":"Person","name":"Juanita S Lopez"},{"@type":"Person","name":"Mohammed M Milhem"},{"@type":"Person","name":"Christian U Blank"},{"@type":"Person","name":"Irene Reijers"},{"@type":"Person","name":"Fiona Thistlethwaite"},{"@type":"Person","name":"Ruth Plummer"},{"@type":"Person","name":"Sarina A Piha-Paul"},{"@type":"Person","name":"Pasi A Jänne"},{"@type":"Person","name":"Elaine Shum"},{"@type":"Person","name":"Heather M Shaw"},{"@type":"Person","name":"Philip R Debruyne"},{"@type":"Person","name":"Cristopher Lao"},{"@type":"Person","name":"Jean-Francois Baurain"},{"@type":"Person","name":"Jennifer H Choe"},{"@type":"Person","name":"Eelke Gort"},{"@type":"Person","name":"Yujie Zhao"},{"@type":"Person","name":"Guy Jerusalem"},{"@type":"Person","name":"Patrick Schöffski"},{"@type":"Person","name":"Andrew William Chen"},{"@type":"Person","name":"Eric A Cohen"},{"@type":"Person","name":"Walter C Mankowski"},{"@type":"Person","name":"Leonid Roshkovan"},{"@type":"Person","name":"Sharyn I Katz"},{"@type":"Person","name":"Despina Kontos"},{"@type":"Person","name":"Lauren K Brady"},{"@type":"Person","name":"Mohammed Qutaish"},{"@type":"Person","name":"Patricia Garrido Castro"},{"@type":"Person","name":"Nora Pencheva"},{"@type":"Person","name":"Gaurav Bajaj"},{"@type":"Person","name":"Yali Fu"},{"@type":"Person","name":"Kristian Windfeld"},{"@type":"Person","name":"Panagiota Reiter"},{"@type":"Person","name":"Maria Jure-Kunkel"},{"@type":"Person","name":"Brandon W Higgs"},{"@type":"Person","name":"Katayoun I Amiri"},{"@type":"Person","name":"Tahamtan Ahmadi"},{"@type":"Person","name":"Ulf Forssmann"},{"@type":"Person","name":"Suresh S Ramalingam"},{"@type":"Person","name":"Ignace Vergote"}],"datePublished":"2025","isPartOf":{"@type":"Periodical","name":"Cancer research communications"},"identifier":"https://doi.org/10.1158/2767-9764.CRC-25-0359","description":"Abstract\n \n Purpose:\n 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.\n \n \n Patients and Methods:\n 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.\n \n \n Results:\n 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.\n \n \n Conclusions:\n 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.\n \n \n Significance:\n 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.\n ","url":"https://innscience.ca/es/community/literature/c3c5f77f-025f-401f-b836-9a8a04e69dcc"}