Journal article
Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients With Advanced Solid Tumors
Cancer research communications, Vol.5(11), pp.2066-2078
11/2025
DOI: 10.1158/2767-9764.CRC-25-0359
PMCID: PMC12648153
PMID: 41166388
Abstract
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 safety and preliminary efficacy of EnaV in solid tumors.
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 maximum tolerated dose (MTD) (dose escalation) and safety (dose expansion). Pharmacokinetic profile, antitumor activity, and AXL expression were also assessed.
During dose escalation, 32 patients received EnaV Q3W; 15 received EnaV 3Q4W. MTD 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 4.5-12.5% with Q3W schedule and from 9.1-11.5% with 3Q4W dose schedule. Disease control rates for NSCLC cohorts were 40.9-50.0%. NSCLC subset analysis demonstrated correlation between radiomics signature and disease control. The relationship between clinical activity and AXL expression was not apparent.
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.
Details
- Title: Subtitle
- Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients With Advanced Solid Tumors
- Creators
- Kristoffer Staal Rohrberg - RigshospitaletJuanita S Lopez - Institute of Cancer ResearchMohammed M Milhem - University of Iowa Hospitals and ClinicsChristian U Blank - The Netherlands Cancer InstituteIrene Reijers - The Netherlands Cancer InstituteFiona Thistlethwaite - The Christie NHS Foundation TrustRuth Plummer - Newcastle UniversitySarina A Piha-Paul - The University of Texas MD Anderson Cancer CenterPasi A Janne - Dana-Farber Cancer InstituteElaine Shum - NYU Langone’s Laura and Isaac Perlmutter Cancer CenterHeather M Shaw - UCL Biomedical Research CentrePhilip R Debruyne - AZ GroeningeChristopher Lao - U-M Rogel Cancer CenterJean-Francois Baurain - Cliniques Universitaires Saint-LucJennifer H Choe - Vanderbilt University Medical CenterEelke Gort - University Medical Center UtrechtYujie Zhao - Mayo Clinic in FloridaGuy Jerusalem - University of LiègePatrick Schöffski - KU LeuvenAndrew William Chen - University of PennsylvaniaEric A Cohen - Columbia UniversityWalter C Mankowski - Columbia UniversityLeonid Roshkovan - University of PennsylvaniaSharyn I Katz - University of PennsylvaniaDespina Kontos - Columbia University Irving Medical CenterLauren K Brady - Genmab (United States)Mohammed Qutaish - Genmab (United States)Patricia Garrido Castro - Genmab (Netherlands)Nora Pencheva - Genmab (Netherlands)Gaurav Bajaj - Genmab (United States)Yali Fu - Genmab (Netherlands)Kristian Windfeld - Genmab (Denmark)Panagiota Reiter - Winship Cancer InstituteMaria Jure-Kunkel - Genmab (United States)Brandon W Higgs - Genmab (United States)Katayoun I Amiri - Genmab (Netherlands)Tahamtan Ahmadi - Genmab (United States)Ulf Forssmann - Genmab (United States)Suresh S Ramalingam - Emory UniversityIgnace Vergote - Universitair Ziekenhuis Leuven
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.5(11), pp.2066-2078
- DOI
- 10.1158/2767-9764.CRC-25-0359
- PMID
- 41166388
- PMCID
- PMC12648153
- NLM abbreviation
- Cancer Res Commun
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Publisher
- American Association for Cancer Research
- Grant note
- Genmab (Genmab A/S)
We acknowledge and thank the patients and their families for their participation in this study. We also acknowledge and thank all the participating study sites, investigators, the data monitoring committee, and other research personnel for their support of this trial. Medical writing and editorial assistance were provided by Amy Zannikos, PharmD, of Peloton Advantage, an OPEN Health company, and funded by Genmab A/S. This study was funded by Genmab.
- Language
- English
- Electronic publication date
- 10/30/2025
- Date published
- 11/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985024141802771
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