A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201)

AGAVE-201, A Phase 2, Open-label, Randomized, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Axatilimab at 3 Different Doses in Patients With Recurrent or Refractory Active Chronic Graft Versus Host Disease Who Have Received at Least 2 Lines of Systemic Therapy

This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: Axatilimab

Detailed Description

AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab in participants with recurrent or refractory active cGVHD after failure of at least 2 prior lines of systemic therapy due to progression of disease, intolerability, or toxicity.

Participants will be randomized to receive 1 of 3 different axatilimab treatment regimens in 28-day treatment cycles for up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Westmead, Australia
    • Westmead Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital
• Belgium
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
  • Roeselare, Belgium
    • AZ Delta
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health Authority
  • Ontario
    • Toronto, Ontario, Canada
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Center - Research Institute
• France
  • Nancy, France
    • CHRU de Nancy - Hôpitaux de Brabois
  • Nantes, France
    • CHU de Nantes - Hotel-Dieu
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75013
    • Hôpital Pitié Salpetrière
  • Pessac, France
    • CHU Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie
  • Pierre-Bénite, France
    • HCL Centre Hospitalier Lyon Sud
  • Auvergne-Rhône-Alpes
    • La Tronche, Auvergne-Rhône-Alpes, France, 38700
      • CHU de Grenoble
  • Grand Est
    • Strasbourg, Grand Est, France, 67200
      • Institut de cancérologie Strasbourg Europe (ICANS)
  • Haure-Garrone
    • Toulouse, Haure-Garrone, France, 31100
      • IUCT-Oncopole
  • Hauts-de-France
    • Amiens, Hauts-de-France, France, 80054
      • Chu Amiens Picardie - Hopital Sud
    • Lille, Hauts-de-France, France, 59037
      • CHRU de Lille - Hopital Claude Huriez
• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus Dresden
  • Jena, Germany, 07740
    • Universitaetsklinikum Jena
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
• Greece
  • Athens, Greece
    • University Hospital of West Attica - Attikon - Hematology Division
  • Pátrai, Greece, 26500
    • University General Hospital of Patras
  • Thessaloniki
    • Eksochi, Thessaloniki, Greece, 57010
      • General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center Ein Karem
  • Ramat Gan, Israel, 5262160
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Brescia, Italy
    • ASST degli Spedali Civili di Brescia
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Monza, Italy
    • ASST di Monza-Ospedale San Gerardo
  • Monza, Italy
    • Fondazione Monza e Brianza per il Bambino e la sua Mamma
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Roma, Italy, 168
    • Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
  • Torino, Italy
    • AOU Città della Salute e della Scienza di Torino - Ospedale Regina Margherita
  • Torino, Italy
    • Citta della Salute e della Scienza di Torino - Ospedale le Molinette
• Poland
  • Gliwice, Poland, 44-102
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
• Portugal
  • Lisbon, Portugal, 1099-023
    • Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)
  • Porto, Portugal
    • Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore
    • Singapore General Hospital
  • Singapore, Singapore, 229899
    • KK Women's and Children hospital
• South Korea
  • Busan, South Korea
    • Pusan National University Hospital
  • Seoul, South Korea
    • Korea University Anam Hospital
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 8032
    • Hospital Clínic Barcelona
  • Donostia / San Sebastian, Spain
    • Hospital Universitario Donostia
  • Granada, Spain, 18014
    • Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Santander, Spain
    • Hospital Universitario Marquis de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Seville
    • Seville, Seville, Spain, 41013
      • Hospital Universitario Virgen del Rocio
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Royal Hospital for Children
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • Royal Marsden Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham - Children's of Alabama
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90059
      • University of California, Los Angeles (UCLA) - Medical Center
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida (UF)
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32806
      • AdventHealth Orlando
    • Tampa, Florida, United States, 33612
      • Moffitt
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center (UCMC)
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Indianapolis
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Johns Hopkins Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48084
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10022
      • Weill Medical College of Cornell University
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
    • Lyndhurst, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma - Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center - Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
    • Salt Lake City, Utah, United States, 84111
      • Intermountain Healthcare
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Carbone Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be 2 years of age or older, at the time of signing the informed consent.
2. Participants who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.

3. Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy.

   • Refractory disease defined as meeting any of the following criteria:

     • The development of 1 or more new sites of disease while being treated for cGVHD.
     • Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD.
     • Participants who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required.
   • Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
4. Participants may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
5. Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged <16 years)
6. Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
7. Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
8. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
10. Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Has acute GVHD without manifestations of cGVHD.
2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
3. History of acute or chronic pancreatitis.
4. History of myositis.
5. History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
6. Participants with acquired immune deficiency syndrome (AIDS).
7. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C [HCV] antibody with positive HCV ribonucleic acid [RNA]).
8. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
9. Female participant who is pregnant or breastfeeding.
10. Previous exposure to CSF1-R targeted therapies.
11. Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
12. For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
13. Receiving another investigational treatment within 28 days of randomization.
14. Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axatilimab Dose Cohort 1; Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.	Drug: Axatilimab; Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.; Other Names: SNDX-6352; Niktimvo
Experimental: Axatilimab Dose Cohort 2; Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.	Drug: Axatilimab; Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.; Other Names: SNDX-6352; Niktimvo
Experimental: Axatilimab Dose Cohort 3; Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.	Drug: Axatilimab; Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.; Other Names: SNDX-6352; Niktimvo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD)	The ORR was defined as the percentage of participants with objective response (complete response [CR] or partial response [PR]). CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site.	First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ-specific Response Rate	Organ-specific response is defined as the number of participants with objective response for the nine individual organs based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal [GI], lower GI, liver, lungs and joints and fascia).	Up to 2 years
ORR on Study as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD		Up to 2 years
Number of Participants With a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale		Up to 2 years
Duration of Response	Duration of response is defined as the time from initial partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.	Up to 2 years
Sustained Response Rate	Sustained response rate is defined as the number of participants with objective response lasting for at least 20 weeks (140 days) from the time of initial response. Responses will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD.	Up to 2 years
Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD		Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid		Up to 2 years
Number of Participants Who Discontinue Corticosteroid Use		Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI)		Up to 2 years
Number of Participants Who Discontinue CNIs		Up to 2 years
Change From Baseline in Circulating Monocyte Number and Phenotype (CD14/16)		Baseline, up to 2 years
Number of Participants With Anti-Drug Antibody		Up to 2 years
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Measurable Concentration (AUC0-t)		Approximately 12 months
Number of Participants With Treatment-emergent Adverse Events		Up to 2 years
Change From Baseline in Bone Turnover Markers		Baseline, up to 2 years
Change From Baseline in Bone Density		Baseline, up to 2 years
Change From Baseline in Colony Stimulating Factor 1 (CSF-1) and Interleukin 34 (IL-34) Levels		Baseline, up to 2 years

Collaborators and Investigators

• Sponsor: Syndax Pharmaceuticals
• Investigators: Study Director: Vedran Radojcic, M.D., Syndax Pharmaceuticals

Publications and helpful links

General Publications

• Wolff D, Cutler C, Lee SJ, Pusic I, Bittencourt H, White J, Hamadani M, Arai S, Salhotra A, Perez-Simon JA, Alousi A, Choe H, Kwon M, Bermudez A, Kim I, Socie G, Chhabra S, Radojcic V, O'Toole T, Tian C, Ordentlich P, DeFilipp Z, Kitko CL; AGAVE-201 Investigators. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024 Sep 19;391(11):1002-1014. doi: 10.1056/NEJMoa2401537.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): April 7, 2023
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: GVHD; cGVHD; graft versus host disease; AGAVE-201; graft-versus-host-disease
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; axatilimab
• Other Study ID Numbers: SNDX-6352-0504; 2024-512978-99-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No