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

NCT04710576 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: SNDX-6352-05042024-512978-99-00
• Study Type: interventional
• Target: 241
• Locations: 16 countries
• Sites: 121

Brief Summary

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.

Conditions

Chronic Graft-versus-host-disease

Keywords

cGVHD; AGAVE-201; GVHD; graft versus host disease; graft-versus-host-disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• 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

  Up to 2 years

• Sustained Response Rate

  Up to 2 years

• Organ-specific Response Rate

  Up to 2 years

Study Arms (3)

Axatilimab Dose Cohort 1

EXPERIMENTAL

Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.

Drug: Axatilimab

Axatilimab Dose Cohort 2

EXPERIMENTAL

Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.

Drug: Axatilimab

Axatilimab Dose Cohort 3

EXPERIMENTAL

Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.

Drug: Axatilimab

Interventions

Axatilimab DRUG

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.

Also known as: Niktimvo, SNDX-6352

Axatilimab Dose Cohort 1; Axatilimab Dose Cohort 2; Axatilimab Dose Cohort 3

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be 2 years of age or older, at the time of signing the informed consent.
• 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.
• 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.
• 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.
• Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
• Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
• Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• 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.
• Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Has acute GVHD without manifestations of cGVHD.
• Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• History of acute or chronic pancreatitis.
• History of myositis.
• 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.
• Participants with acquired immune deficiency syndrome (AIDS).
• 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 \[RNA\]).
• 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).
• Female participant who is pregnant or breastfeeding.
• Previous exposure to CSF1-R targeted therapies.
• Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
• 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.
• Receiving another investigational treatment within 28 days of randomization.
• 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).

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (121)

University of Alabama at Birmingham - Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles (UCLA) - Medical Center

Los Angeles, California, 90059, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida (UF)

Gainesville, Florida, 32610, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

AdventHealth Orlando

Orlando, Florida, 32806, United States

Location

Moffitt

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, 60637, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Franciscan Health Indianapolis

Indianapolis, Indiana, 46237, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21231-2410, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48084, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Weill Medical College of Cornell University

New York, New York, 10022, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

The Cleveland Clinic Foundation

Lyndhurst, Ohio, 44195, United States

Location

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Intermountain Healthcare

Salt Lake City, Utah, 84111, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Westmead Hospital

Westmead, Australia

Location

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

AZ Delta

Roeselare, Belgium

Location

Vancouver Coastal Health Authority

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

McGill University Health Center - Research Institute

Montreal, Quebec, H3G 1A4, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

CHU de Grenoble

La Tronche, Auvergne-Rhône-Alpes, 38700, France

Location

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, Grand Est, 67200, France

Location

IUCT-Oncopole

Toulouse, Haure-Garrone, 31100, France

Location

CHU Amiens Picardie - Hopital Sud

Amiens, Hauts-de-France, 80054, France

Location

CHRU de Lille - Hopital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

CHRU de Nancy - Hôpitaux de Brabois

Nancy, France

Location

CHU de Nantes - Hôtel-Dieu

Nantes, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital Pitie Salpetriere

Paris, 75013, France

Location

CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie

Pessac, France

Location

HCL Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Universitaetsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Jena

Jena, 07740, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz

Mainz, 55131, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Universitatsklinikum Regensburg

Regensburg, 93053, Germany

Location

General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit

Eksochi, Thessaloniki, 57010, Greece

Location

University Hospital of West Attica - Attikon - Hematology Division

Athens, Greece

Location

University General Hospital of Patras

Pátrai, 26500, Greece

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah Medical Center Ein Karem

Jerusalem, 9112001, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5262160, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

ASST degli Spedali Civili di Brescia

Brescia, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

ASST di Monza-Ospedale San Gerardo

Monza, Italy

Location

Fondazione Monza e Brianza per il Bambino e la sua Mamma

Monza, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, 168, Italy

Location

AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita

Torino, Italy

Location

Citta della Salute e della Scienza di Torino - Ospedale le Molinette

Torino, Italy

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii

Gliwice, 44-102, Poland

Location

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)

Lisbon, 1099-023, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, Portugal

Location

National University Hospital

Singapore, 119074, Singapore

Location

KK Women's and Children hospital

Singapore, 229899, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Pusan National University Hospital

Busan, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Hospital Universitario Virgen del Rocio

Seville, Seville, 41013, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 8032, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Spain

Location

Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marquis de Valdecilla

Santander, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, United Kingdom

Location

Royal Marsden Foundation Trust

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39292927 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

axatilimab

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Syndax Pharmaceuticals

clinicaltrials@syndax.com

781-419-1400

Study Officials

• Vedran Radojcic, M.D.

  Syndax Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 14, 2021
• Study Start: March 4, 2021
• Primary Completion: April 7, 2023
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 16, 2026
• Results First Posted: October 10, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11); AU (2); TW (3); BE (2); US (47); PT (2); GR (3); SG (3); IT (10); KR (4); CA (4); IL (4); ES (13); DE (6); PL (1); GB (6)