Evidence map›Paper›PMID 41166388›Full record

Trial reportCancer research communications2025

Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors.

Kristoffer Staal Rohrberg, Juanita S Lopez, Mohammed M Milhem, Christian U Blank, Irene Reijers, Fiona Thistlethwaite, Ruth Plummer, Sarina A Piha-Paul, Pasi A Jänne, Elaine Shum and 30 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Cancers · 2026
    Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Kristoffer Staal RohrbergDepartment of Oncology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.ORCID 0000-0002-5448-9003
Juanita S LopezDrug Development Unit, Royal Marsden Hospital/Institute of Cancer Research, Sutton, United Kingdom.ORCID 0000-0001-8321-4212
Mohammed M MilhemDepartment of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.ORCID 0000-0003-4663-6824
Christian U BlankDivision of Molecular Oncology and Immunology, Department of Medical Oncology, Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands.ORCID 0000-0002-7945-5846
Irene ReijersDivision of Molecular Oncology and Immunology, Department of Medical Oncology, Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands.ORCID 0000-0002-7103-3219
Fiona ThistlethwaiteThe Christie NHS Foundation Trust and Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-4832-7008
Ruth PlummerNewcastle University, Newcastle upon Tyne, United Kingdom.ORCID 0000-0003-0107-1444
Sarina A Piha-PaulDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9455-1660
Pasi A JänneLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-7821-4928
Elaine ShumMedical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0000-0002-0390-5716
Heather M ShawNational Institute for Health Research (NIHR) University College London Hospitals (UCLH) Clinical Research Facility, National Health Service (NHS) Foundation Trust, London, United Kingdom.ORCID 0000-0002-6545-2927
Philip R DebruyneDepartment of Medical Oncology, Kortrijk Cancer Centre, AZ Groeninge, Kortrijk, Belgium.ORCID 0000-0001-5438-9697
Cristopher LaoDivision of Hematology Oncology, Department of Internal Medicine, Rogel Cancer Center, Ann Arbor, Michigan.ORCID 0000-0002-5952-7267
Jean-Francois BaurainDepartment of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, UC Louvain and Institute for Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0003-4876-4600
Jennifer H ChoeDivision of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.ORCID 0000-0002-9279-0235
Eelke GortDepartment of Medical Oncology, UMC Utrecht Cancer Center, Utrecht, the Netherlands.ORCID 0000-0001-7390-0761
Yujie ZhaoDepartment of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida.ORCID 0000-0002-3214-2658
Guy JerusalemMedical Oncology Department, CHU Liège and Liège University, Liege, Belgium.ORCID 0000-0002-8845-0043
Patrick SchöffskiGeneral Medical Oncology, University Hospitals Leuven, Leuven, Belgium.ORCID 0000-0001-5980-030X
Andrew William ChenDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-7781-1109
Eric A CohenDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-5067-8835
Walter C MankowskiDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-8591-6592
Leonid RoshkovanDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-8890-8835
Sharyn I KatzDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-9816-2291
Despina KontosDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-9031-5126
Lauren K BradyGenmab US., Plainsboro, New Jersey.ORCID 0009-0006-3012-8509
Mohammed QutaishGenmab US., Plainsboro, New Jersey.ORCID 0000-0002-6707-2872
Patricia Garrido CastroGenmab B.V., Utrecht, the Netherlands.ORCID 0009-0000-6618-0479
Nora PenchevaGenmab B.V., Utrecht, the Netherlands.ORCID 0009-0006-4689-1218
Gaurav BajajGenmab US., Plainsboro, New Jersey.ORCID 0000-0003-0298-4659
Yali FuGenmab US., Plainsboro, New Jersey.ORCID 0009-0009-3115-5578
Kristian WindfeldGenmab A/S, Copenhagen, Denmark.ORCID 0009-0004-3313-3923
Panagiota ReiterGenmab A/S, Copenhagen, Denmark.ORCID 0009-0006-5597-1252
Maria Jure-KunkelGenmab US., Plainsboro, New Jersey.ORCID 0000-0002-3751-1934
Brandon W HiggsGenmab US., Plainsboro, New Jersey.ORCID 0000-0002-2951-0245
Katayoun I AmiriGenmab US., Plainsboro, New Jersey.ORCID 0009-0002-7254-5977
Tahamtan AhmadiGenmab US., Plainsboro, New Jersey.ORCID 0009-0007-5031-3792
Ulf ForssmannGenmab A/S, Copenhagen, Denmark.ORCID 0009-0008-2534-675X
Suresh S RamalingamDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, Georgia.ORCID 0000-0002-0757-3106
Ignace VergoteDepartment of Gynecology and Obstetrics, Gynecologic Oncology, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium.ORCID 0000-0002-7589-8981

Funding

Genmab (Genmab A/S)
6 · The paper itself

Abstract

purposeAXL, 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

methodsThis 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.

resultsDuring 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.

conclusionsEnaV 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.

Indexed as

ImmunoconjugatesNeoplasmsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAdultAgedAged, 80 and overAxl Receptor Tyrosine KinaseFemaleHumansMaleMaximum Tolerated DoseMiddle AgedOligopeptidesAXL protein, humanAxl Receptor Tyrosine KinaseImmunoconjugatesOligopeptidesProto-Oncogene ProteinsReceptor Protein-Tyrosine Kinases

Identifiers

PMID41166388
PMCPMC12648153

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.