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

NCT06821542 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: INCA034176-3552024-518973-32-00
• Study Type: interventional
• Target: 9
• Locations: 16 countries
• Sites: 130

Brief Summary

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.

Conditions

Chronic Graft-versus-host-disease

Keywords

cGVHD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Failure-free survival (FFS)

  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

  12 months

• Best Overall Response (BOR)

  Up to 5 years

• DOR (in responders only)

  Up to 5 years

Study Arms (2)

Axatilimab

EXPERIMENTAL

Axatilimab at the protocol-defined dose.

Drug: INCA034176

Best available Treatment (BAT)

EXPERIMENTAL

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)

Interventions

INCA034176 DRUG

IV infusion

Also known as: Axatilimab

Axatilimab

Best Available Therapy (BAT) DRUG

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.

Also known as: 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

Best available Treatment (BAT)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (130)

Medical University of Graz

Graz, 08036, Austria

Location

Medizinische Universitaet Innsbruck - Universitaetsklinik Fuer Innere Medizin Iii

Innsbruck, 06020, Austria

Location

Krankenhaus Der Elisabethinen Linz Gmbh

Linz, 04020, Austria

Location

Medizinische Universitat Wien, Universitatsklinik Fur Innere Medizin I

Vienna, 01090, Austria

Location

St. Anna Childrens Hospital

Vienna, 01090, Austria

Location

Az Sint-Jan Brugge Av

Bruges, 08000, Belgium

Location

Chu Ucl Namur Site Godinne

Godinne-mont, 05530, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 03000, Belgium

Location

Chu Liege -Centre Hospitalier Universitaire Sart Tilman

Liège, 04000, Belgium

Location

Algemeen Ziekenhuis Delta

Roeselare, 08800, Belgium

Location

Universite Catholique de Louvain (Ucl) - Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, 01200, Belgium

Location

Fakultni Nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava-poruba, 708 52, Czechia

Location

Ustav Hematologie A Krevni Transfuze (Uhkt), the Institute of Hematology and Blood Transfusion (Ihbt

Prague, 12808, Czechia

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

New Children'S Hospital, University of Helsinki and Helsinki University Hospital

Helsinki, 00290, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Chu D'Amiens-Picardie - Hopital Sud

Amiens, 80054, France

Location

CHU CAEN

Caen, 14000, France

Location

Centre Hospitalier Regional Universitaire (Chru) de Lille - Hopital Claude Huriez

Lille, 59037, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Chu de Nantes

Nantes, 44000, France

Location

Centre Hospitalier Universitaire de Nice,Hopital L Archet

Nice, 06200, France

Location

Hospital Saint-Louis - Aphp

Paris, 75010, France

Location

Hopital Universitaire Robert Debre

Paris, 75019, France

Location

Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque

Pessac, 33600, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut Claudius Regaud Cancer Comprehensive Center - Iuct Oncopole

Toulouse, 31059, France

Location

Chru Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Gustave Roussy Cancer Campus Grand Paris- (Institut de Cancerologie Gustave-Roussy)

Villejuif, 94805, France

Location

Uniklinik Rwth Aachen Medizinische Klinik Iv

Aachen, 52074, Germany

Location

Charite - Universitaetsmedizin Berlin

Berlin, 10117, Germany

Location

Universitaetsklinikum Koeln

Cologne, 50937, Germany

Location

University Hospital Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitatsklinikum Erlangen

Erlangen, 91054, Germany

Location

Klinikum Der Johann Wolfgang Goethe-Universitaet

Frankfurt am Main, 60590, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsmedizin Goettingen

Göttingen, 37075, Germany

Location

Universitaetsklinikum Halle

Halle, 06120, Germany

Location

Universitaetsklinikum Des Saarlandes

Homburg, 66421, Germany

Location

Universitaetsklinikum Schleswig-Holstein, Uksh-Campus Kiel

Kiel, 24105, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii

Mainz, 55131, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

University Clinic Regensburg

Regensburg, 93053, Germany

Location

University Hospital of Ulm, Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

University of Wuerzburg

Würzburg, 97080, Germany

Location

General Hospital of Athens Evangelismos - Eye Hospital

Athens, 10676, Greece

Location

Attikon Hospital and Cutaneous Lymphoma Clinic-Athens University Medical School

Athens, 12462, Greece

Location

University Hospital of Patras

RIO Patras, 26504, Greece

Location

General Hospital of Thessalonikis George Papanikolaou - Gene and Cell Therapy Center

Thessaloniki, 57010, Greece

Location

St. James Hospital

Dublin, D08 NHY1, Ireland

Location

Ss Antonio & Biagio and C. Arrigo Hospital

Alessandria, 15121, Italy

Location

Azienda Ospedaliero Universitaria Delle Marche Clinica Ematologica

Ancona, 60126, Italy

Location

Azienda Ospedaliera Papa Giovanni Xxiii

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S. Orsola-Malpighi - Istituto Di Ematolog

Bologna, 40138, Italy

Location

Universita Degli Studi Di Brescia - Azienda Ospedaliera Spedali Civili Di Brescia

Brescia, 25123, Italy

Location

Azienda Policlinico Vittorio Emanuele, Presidio G Rodolico, Universita Di Catania

Catania, 95125, Italy

Location

Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica

Florence, 50134, Italy

Location

Irccs - Azienda Ospedaliera Universitaria - Ist San Martino

Genova, 16132, Italy

Location

Pia Fondazione Cardinale Giovanni Panico Azienda Ospedaliera

Lecce, 73039, Italy

Location

Fondazione Irccs Ca' Granda - Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) - Ospedale San Raffaele (Hsr) (Istituto

Milan, 20132, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera San Gerardo Di Monza

Monza, 20900, Italy

Location

Azienda Ospedaliera Di Rilievo Nazionale (Aorn) 'Antonio Cardarelli'

Naples, 80131, Italy

Location

Azienda Ospedaliero Universitaria Federico Ii Di Napoli

Naples, 80131, Italy

Location

Azienda Ospedale Universita Di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello

Palermo, 90146, Italy

Location

Irccs Fondazione Policlinico San Matteo

Pavia, 27100, Italy

Location

Presidio Ospedaliero Spirito Santo Azienda U.S.L. Pescara

Pescara, 65124, Italy

Location

Morelli Hospital

Reggio Calabria, 89133, Italy

Location

Aou Policlinico Umberto I

Roma, 00161, Italy

Location

A. Gemelli University Hospital, Catholic University of the Sacred Heart

Roma, 00168, Italy

Location

Fondazione Ptv Policlinico Tor Vergata

Rome, 00133, Italy

Location

Irccs Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

Location

Irccs Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Fondazione Ircss Casa Sollievo Della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

A.O.U. Citta Della Salute E Della Scienza Di Torino

Torino, 10126, Italy

Location

Ospedale Santa Maria Di Ca' Foncello

Treviso, 31100, Italy

Location

Clinica Ematologica, Dism Azienda Ospedaliero Universitaria

Udine, 33100, Italy

Location

Uoc Ematologia E Centro Trapianti Midollo Osseo Br, Ospedale Borgo Roma

Verona, 37134, Italy

Location

Amsterdam University Medical Center (Amsterdam Umc), Vrije University Medical Center (Vumc)

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Leiden University Medical Center (Leids Universitair Medisch Centrum (Lumc))

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center (Mumc)

Maastricht, 6229 HX, Netherlands

Location

Erasmus Medisch Centrum 1

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht (Umc Utrecht)

Utrecht, 3584 CX, Netherlands

Location

Haukeland University Hospital

Bergen, 05021, Norway

Location

Rikshospitalet University Hospital

Oslo, 00027, Norway

Location

Ipo Lisboa Francisco Gentil

Lisbon, 1099-035, Portugal

Location

Centro Hospitalar Universitario Lisboa Norte Epe

Lisbon, 1649-028, Portugal

Location

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E

Porto, 4200-072, Portugal

Location

Institut Catala D'Oncologia Badalona, Hospital Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona (Hospital Clinic I Provincial)

Barcelona, 08036, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Institut Catala D Oncologia

Barcelona, 08908, Spain

Location

Hospital Clinico Universitario Virgen de La Arrixaca

El Palmar, 30120, Spain

Location

Hospital Sant Joan de Deu Barcelona - Children'S Hospital

Esplugues de Llobregat, 08950, Spain

Location

Hospital Universitario Virgen de Las Nieves

Granada, 18014, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital General Universitario Gregorio Maranon (Hgugm)

Madrid, 28007, Spain

Location

Hospital Universitario Infantil Nino Jesus

Madrid, 28009, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Donostia

SAN Sebasttian, 20014, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia (Instituto de Investigacion Sanitaria Incliva)

Valencia, 46010, Spain

Location

Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

University of Gothenburg and Queen Silvia Children S Hospital At Sahlgrenska University Hospital

Gothenburg, 41650, Sweden

Location

Skanes Universitetssjukhus - Universitetssjukhuset I Lund

Lund, 221 85, Sweden

Location

Karolinska Universitetssjukhuset, Centrum For Cellterapi Och Allogen Stamcellstransplantation

Stockholm, 14186, Sweden

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

University Hospital Basel

Basel, 04031, Switzerland

Location

Hopitaux Universitaires de Geneve (Hug) - Centre de Recherche Clinique (Crc)

Geneva, 01205, Switzerland

Location

Universitatsspital Zurich

Zurich, 08091, Switzerland

Location

Universitats-Kinderspital Zurich Eleonorenstiftung

Zurich, CH-8032, Switzerland

Location

Cardiff and Vale Nhs Trust - University Hospital of Wales (Uhw)

Cardiff, CF14 4XW, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

St James'S University Hospital - Leeds Teaching Hospitals Nhs Trust

Leeds, LS9 7TF, United Kingdom

Location

University Hospitals of Leicester Nhs Trust-Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

King'S College Hospital Nhs Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related 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

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

axatilimab; Calcineurin Inhibitors; Cyclosporine; Tacrolimus; Photopheresis; Mycophenolic Acid; Everolimus; Sirolimus; Rituximab; Pentostatin; Proteasome Inhibitors; Imatinib Mesylate; ibrutinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Protease Inhibitors; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Study Officials

• Incyte Medical Monitor

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 12, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): November 30, 2032
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

ES (21); NO (2); PT (3); DE (17); BE (6); IT (31); FR (14); CZ (3); FI (3); IE (1); AU (5); SE (5); CH (4); NL (6); GR (4); GB (5)