A Study to Evaluate Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy

A Phase 3, Randomized, Open-Label Study of Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy

This study will be conducted to compare Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: INCA034176; Drug: Best Available Therapy (BAT)

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 08036
    • Medical University of Graz
  • Innsbruck, Austria, 06020
    • Medizinische Universitaet Innsbruck - Universitaetsklinik Fuer Innere Medizin Iii
  • Linz, Austria, 04020
    • Krankenhaus Der Elisabethinen Linz Gmbh
  • Vienna, Austria, 01090
    • Medizinische Universitat Wien, Universitatsklinik Fur Innere Medizin I
  • Vienna, Austria, 01090
    • St. Anna Childrens Hospital
• Belgium
  • Bruges, Belgium, 08000
    • Az Sint-Jan Brugge Av
  • Godinne-mont, Belgium, 05530
    • CHU UCL Namur site Godinne
  • Leuven, Belgium, 03000
    • Universitair Ziekenhuis Leuven
  • Liège, Belgium, 04000
    • Chu Liege -Centre Hospitalier Universitaire Sart Tilman
  • Roeselare, Belgium, 08800
    • Algemeen Ziekenhuis Delta
  • Woluwe-Saint-Lambert, Belgium, 01200
    • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Fakultní nemocnice Hradec Králové
  • Ostrava-poruba, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Prague, Czechia, 12808
    • Ustav Hematologie A Krevni Transfuze (Uhkt), the Institute of Hematology and Blood Transfusion (Ihbt
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital
  • Helsinki, Finland, 00290
    • New Children'S Hospital, University of Helsinki and Helsinki University Hospital
  • Turku, Finland, 20520
    • Turku University Hospital
• France
  • Amiens, France, 80054
    • CHU d'Amiens-Picardie - Hôpital Sud
  • Caen, France, 14000
    • CHU Caen
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire (Chru) de Lille - Hopital Claude Huriez
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44000
    • CHU de Nantes
  • Nice, France, 06200
    • Centre Hospitalier Universitaire de Nice,Hopital L Archet
  • Paris, France, 75019
    • Hopital Universitaire Robert Debre
  • Paris, France, 75010
    • Hospital Saint-Louis - Aphp
  • Pessac, France, 33600
    • Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Toulouse, France, 31059
    • Institut Claudius Regaud Cancer Comprehensive Center - Iuct Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • Chru Nancy
  • Villejuif, France, 94805
    • Gustave Roussy Cancer Campus Grand Paris- (Institut de Cancerologie Gustave-Roussy)
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH Aachen Medizinische Klinik IV
  • Berlin, Germany, 10117
    • Charité - Universitaetsmedizin Berlin
  • Cologne, Germany, 50937
    • Universitaetsklinikum Koeln
  • Dresden, Germany, 01307
    • University Hospital Carl Gustav Carus
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Frankfurt am Main, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Freiburg im Breisgau, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Göttingen, Germany, 37075
    • Universitaetsmedizin Goettingen
  • Halle, Germany, 06120
    • Universitaetsklinikum Halle
  • Homburg, Germany, 66421
    • Universitaetsklinikum des Saarlandes
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein, UKSH-Campus Kiel
  • Leipzig, Germany, 04103
    • University Hospital Leipzig
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Regensburg, Germany, 93053
    • University Clinic Regensburg
  • Ulm, Germany, 89081
    • University Hospital Of Ulm, Universitatsklinikum Ulm
  • Würzburg, Germany, 97080
    • University of Wuerzburg
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evangelismos - Eye Hospital
  • Athens, Greece, 12462
    • Attikon Hospital and Cutaneous Lymphoma Clinic-Athens University Medical School
  • RIO Patras, Greece, 26504
    • University Hospital of Patras
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessalonikis George Papanikolaou - Gene and Cell Therapy Center
• Ireland
  • Dublin, Ireland, D08 NHY1
    • St. James Hospital
• Italy
  • Alessandria, Italy, 15121
    • Ss Antonio & Biagio and C. Arrigo Hospital
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Delle Marche Clinica Ematologica
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Azienda Ospedaliera Sant'Orsola Malpighi
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S. Orsola-Malpighi - Istituto Di Ematolog
  • Brescia, Italy, 25123
    • Universita Degli Studi Di Brescia - Azienda Ospedaliera Spedali Civili Di Brescia
  • Catania, Italy, 95125
    • Azienda Policlinico Vittorio Emanuele, Presidio G Rodolico, Universita Di Catania
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
  • Genova, Italy, 16132
    • Irccs - Azienda Ospedaliera Universitaria - Ist San Martino
  • Lecce, Italy, 73039
    • Pia Fondazione Cardinale Giovanni Panico Azienda Ospedaliera
  • Milan, Italy, 20122
    • Fondazione Irccs Ca' Granda - Ospedale Maggiore Policlinico
  • Milan, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
  • Milan, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) - Ospedale San Raffaele (Hsr) (Istituto
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerardo di Monza
  • Naples, Italy, 80131
    • Azienda Ospedaliero Universitaria Federico II di Napoli
  • Naples, Italy, 80131
    • Azienda Ospedaliera Di Rilievo Nazionale (Aorn) 'Antonio Cardarelli'
  • Padova, Italy, 35128
    • Azienda Ospedale Universita Di Padova
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
  • Pavia, Italy, 27100
    • Irccs Fondazione Policlinico San Matteo
  • Pescara, Italy, 65124
    • Presidio Ospedaliero Spirito Santo Azienda U.S.L. Pescara
  • Reggio Calabria, Italy, 89133
    • Morelli Hospital
  • Roma, Italy, 00161
    • AOU Policlinico Umberto I
  • Roma, Italy, 00168
    • A. Gemelli University Hospital, Catholic University of the Sacred Heart
  • Rome, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
  • Rome, Italy, 00133
    • Fondazione PTV Policlinico Tor Vergata
  • Rozzano, Italy, 20089
    • Irccs Istituto Clinico Humanitas
  • San Giovanni Rotondo, Italy, 71013
    • Fondazione Ircss Casa Sollievo Della Sofferenza
  • Torino, Italy, 10126
    • A.O.U. Citta della Salute e della Scienza di Torino
  • Treviso, Italy, 31100
    • Ospedale Santa Maria Di Ca' Foncello
  • Udine, Italy, 33100
    • Clinica Ematologica, Dism Azienda Ospedaliero Universitaria
  • Verona, Italy, 37134
    • Uoc Ematologia E Centro Trapianti Midollo Osseo Br, Ospedale Borgo Roma
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam University Medical Center (Amsterdam UMC), Vrije University Medical Center (VUMC)
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center (Leids Universitair Medisch Centrum (LUMC))
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center (MUMC)
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medisch Centrum 1
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht (Umc Utrecht)
• Norway
  • Bergen, Norway, 05021
    • Haukeland University Hospital
  • Oslo, Norway, 00027
    • Rikshospitalet University Hospital
• Portugal
  • Lisbon, Portugal, 1099-035
    • IPO Lisboa Francisco Gentil
  • Lisbon, Portugal, 1649-028
    • Centro Hospitalar Universitario Lisboa Norte Epe
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E
• Spain
  • Badalona, Spain, 08916
    • Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
  • Barcelona, Spain, 08908
    • Institut Catala D Oncologia
  • El Palmar, Spain, 30120
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Esplugues de Llobregat, Spain, 08950
    • Hospital Sant Joan de Deu Barcelona - Children'S Hospital
  • Granada, Spain, 18014
    • Hospital Universitario Virgen De Las Nieves
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital Universitario de Gran Canaria Doctor Negrín
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28009
    • Hospital Universitario Infantil Nino Jesus
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon (HGUGM)
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • SAN Sebasttian, Spain, 20014
    • Hospital Universitario de Donostia
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia (Instituto de Investigacion Sanitaria Incliva)
  • Valencia, Spain, 46026
    • Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska University Hospital
  • Gothenburg, Sweden, 41650
    • University of Gothenburg and Queen Silvia Children S Hospital At Sahlgrenska University Hospital
  • Lund, Sweden, 221 85
    • Skanes Universitetssjukhus - Universitetssjukhuset I Lund
  • Stockholm, Sweden, 14186
    • Karolinska Universitetssjukhuset, Centrum For Cellterapi Och Allogen Stamcellstransplantation
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital
• Switzerland
  • Basel, Switzerland, 04031
    • University Hospital Basel
  • Geneva, Switzerland, 01205
    • Hopitaux Universitaires de Geneve (Hug) - Centre de Recherche Clinique (Crc)
  • Zurich, Switzerland, 08091
    • Universitätsspital Zürich
  • Zurich, Switzerland, CH-8032
    • Universitats-Kinderspital Zurich Eleonorenstiftung
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Cardiff and Vale Nhs Trust - University Hospital of Wales (Uhw)
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital - Leeds Teaching Hospitals NHS Trust
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester Nhs Trust-Leicester Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 12 years at the time of signing the ICF.
• Active, moderate to severe cGVHD, requiring systemic immune suppression.
• Participants with refractory or recurrent cGVHD who have received at least 2 lines of systemic therapy, including corticosteroids and ruxolitinib.
• Concomitant use of systemic corticosteroids is allowed. Participants on systemic corticosteroids must be on a stable dose of corticosteroids for at least 2 weeks prior to C1D1. Topical and inhaled corticosteroid agents are allowed.
• Participants must accept to be treated with one of the following BAT options on C1D1: CNI (cyclosporine or tacrolimus), ECP, MMF, an mTOR inhibitor (everolimus or sirolimus), rituximab, pentostatin, proteasome inhibitors, imatinib, or ibrutinib.
• History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.

Exclusion Criteria:

• Receipt of more than 1 prior allo-HCT. Prior autologous HCT is allowed.
• Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
• Severe renal impairment, that is, estimated creatinine clearance < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis.
• Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
• History of acute or chronic pancreatitis.
• Active, symptomatic myositis.
• Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axatilimab; Axatilimab at the protocol-defined dose.	Drug: INCA034176; IV infusion; Other Names: Axatilimab
Experimental: Best available Treatment (BAT); Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.	Drug: Best Available Therapy (BAT); Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.; Other Names: BAT could include:; • Calcineurin inhibitor (cyclosporine or tacrolimus); • Extracorporeal photopheresis (ECP); • Mycophenolate mofetil (MMF); • A mammalian target of rapamycin (mTOR) inhibitor (everolimus or sirolimus); • Rituximab; • Pentostatin; • Proteasome inhibitors; • Imatinib; • Ibrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR) at 6 months	Defined for each treatment group as complete response (CR) or partial response (PR) at 6 months (Cycle 7 Day 1, 28-day cycles) in the absence of new systemic therapy for cGVHD. Responses defined by the 2014 NIH consensus criteria.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival (FFS)	Defined as the time from the date of randomization to the date of addition or initiation of another systemic therapy for cGVHD, relapse of underlying disease, or death due to any cause.	Up to 5 years
Proportion of participants with a ≥ 7-point improvement in modified Lee Symptom Scale (mLSS) total score		Up to 5 years
Overall Response at 12 months	Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.	12 months
Best Overall Response (BOR)	Defined as the best response of CR or PR in the first 6 months (up to and including Cycle 7 Day 1), and at any timepoint up to the initiation of new therapy for cGVHD.	Up to 5 years
DOR (in responders only)	Defined as the time from the date of first response (PR or CR) to the date of progression of cGVHD from baseline scoring, start of new systemic treatment for cGVHD, or death from any cause, whichever comes first. An additional measure of response durability will consider DOR as the time from the date of first response to the date of new systemic therapy for cGVHD or death from any cause, whichever occurs first.	Up to 5 years
Organ-specific response	Organ-specific response as defined in the protocol.	Up to 5 years
Overall Survival (OS)	Defined as the time from the date of randomization to the date of death due to any cause.	Up to 5 years
Nonrelapse mortality (NRM)	Defined as the time from the date of randomization to the date of death not preceded by relapse of primary hematologic disease.	Up to 5 years
Time to primary hematologic disease relapse	Defined as the time from the date of randomization to the date of relapse.	Up to 5 years
Percent reduction in daily corticosteroid dose at 6 months		6 months
Proportion of participants who tapered off all corticosteroids at 6 months		6 months
Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment.	Up to 5 years and 30 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Publications and helpful links

Helpful Links

• A Study to Evaluate Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2025
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): November 30, 2032

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: cGVHD
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Fatty Acids; Lipids; Surgical Procedures, Operative; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Polycyclic Compounds; Amides; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pyrimidine Nucleosides; Pyrimidines; Benzene Derivatives; Macrolides; Lactones; Nucleosides; Macrocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Deoxyribonucleosides; Acids, Carbocyclic; Peptides, Cyclic; Benzoates; Caproates; Cyclosporins; Phototherapy; Benzamides; Piperazines; Extracorporeal Circulation; PUVA Therapy; Ultraviolet Therapy; Coformycin; Formycins; Rituximab; Imatinib Mesylate; Everolimus; Sirolimus; Mycophenolic Acid; Tacrolimus; Cyclosporine; Calcineurin Inhibitors; Pentostatin; Proteasome Inhibitors; ibrutinib; axatilimab; Photopheresis
• Other Study ID Numbers: INCA034176-355; 2024-518973-32-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes