Axatilimab for Sclerotic Chronic Graft-versus-Host Disease

NCT07011810 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125196NCI-2025-01612FHIRB0020804
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests how well axatilimab works in treating patients with thickening or hardening (sclerosis) of the skin related to chronic graft-versus-host disease after a donor stem cell transplant. Chronic graft-versus-host disease (cGVHD) remains a major complication of donor stem cell transplants. Sclerosis, while not associated with a higher risk of death, can lead to serious disabilities. Usual treatments for cGVHD can be associated with significant side effects and unsatisfactory outcomes. A monoclonal antibody, like axatilimab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Axatilimab blocks a receptor and depletes cells that may be involved in the development of inflammation and fibrosis in cGVHD. Giving axatilimab may improve or prevent worsening of sclerosis related to cGVHD in patients after a donor stem cell transplant.

Conditions

Chronic Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) in sclerotic manifestations

  Will be defined as the proportion of patients with objective response per 2014 National Institutes of Health (NIH) skin and joint criteria.

  Up to 24 weeks, cycle 7 day 1 (cycle length = 28 days)

Secondary Outcomes (6)

• Failure-free survival

  Up to 2 years

• Modified Lee Symptom Scale summary score

  Up to 2 years

• ORR in sclerotic manifestations

  Up to and at cycle 13 day 1, 48 weeks (cycle length = 28 days)

• Change in patient 0-10 sclerotic scale

  Up to and at cycle 7 day 1 (24 weeks) and cycle 13 day 1 (48 weeks) (cycle length = 28 days)

• Change in clinician 0-10 sclerotic scale

  Up to and at cycle 7 day 1 (24 weeks and cycle 13 day 1 (48 weeks) (cycle length = 28 days)

Study Arms (1)

Treatment (axatilimab)

EXPERIMENTAL

Patients receive axatilimab IV over 30 minutes on days 1 and 15 of cycles 1-6 and then on day 1 of remaining cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Additionally, patients may undergo optional skin biopsies and optional skin flexibility assessments throughout the study.

Biological: Axatilimab; Procedure: Biospecimen Collection; Other: Questionnaire Administration; Procedure: Skin Biopsy; Procedure: Skin Measurement

Interventions

Axatilimab BIOLOGICAL

Given IV

Also known as: Anti-M-CSFR Monoclonal Antibody SNDX-6352, Axatilimab-csfr, INCA 034176, INCA 34176, INCA-034176, INCA-34176, INCA034176, INCA34176, Niktimvo, SNDX 6352, SNDX-6352, SNDX6352, UCB6352

Treatment (axatilimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (axatilimab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (axatilimab)

Skin Biopsy PROCEDURE

Undergo optional skin biopsy

Also known as: Biopsy of Skin

Treatment (axatilimab)

Skin Measurement PROCEDURE

Undergo optional skin flexibility assessment

Also known as: Myoton PRO

Treatment (axatilimab)

Eligibility Criteria

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

You may qualify if:

• Adults aged 18 and older
• Ability to understand and willingness to sign a written informed consent document
• Allogeneic stem cell transplant, with active cGVHD requiring systemic treatment. Active cGVHD is defined as the presence of signs and symptoms of cGVHD diagnosed per the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical trials in cGVHD
• Sclerotic skin score 2-3 or PROM \< 24 due to cGVHD
• Initial diagnosis of sclerosis within the past 24 weeks (168 days)
• No new non-corticosteroid systemic immunosuppressive agent within 28 days prior to screening, unless there is a plan to stop them no later than 21 days after the first dose of axatilimab. Receipt of systemic corticosteroids ≤ 1 mg/kg prednisone or prednisone equivalent daily is allowed at the time of enrollment and may be continued after axatilimab initiation
• If patient has been previously treated with systemic immunosuppression for sclerosis, one of the following two conditions must be true: (a) the systemic immunosuppressive treatment(s) were given for at least 60 days and the sclerotic cGVHD either did not respond or progressed; (b) the systemic immunosuppressive treatment(s) were given for less than 60 days due to lack of sclerotic cGVHD response, sclerotic cGVHD progression, toxicity or logistic reasons and have or will be stopped no later than 21 days after the first dose of axatilimab
• Karnofsky performance status ≥ 60%
• Absolute neutrophil count ≥ 1.0 x 10\^9/L (evaluated during the 28-day screening period)
• Platelet count ≥ 50 x 10\^9/L (evaluated during the 28-day screening period) (without transfusion within 2 weeks of study entry)
• If no suspected or proven liver cGVHD, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (evaluated during the 28-day screening period) unless due to Gilbert's disease
• If no suspected or proven liver cGVHD, total bilirubin ≤ 1.5 x ULN (evaluated during the 28-day screening period) unless due to Gilbert's disease
• For patients with suspected or documented liver cGVHD, ALT and AST ≤ 5 x ULN (evaluated during the 28-day screening period) unless due to Gilbert's disease
• For patients with suspected or documented liver cGVHD, total bilirubin ≤ 1.5 x ULN (evaluated during the 28-day screening period) unless due to Gilbert's disease
• Estimated creatinine clearance ≥ 30 mL/min based on the institutional formula

You may not qualify if:

• Hospitalization for evaluation or management of an infection within 28 days prior to screening
• History or other evidence of significant organ dysfunction that would make the patient, in the opinion of the investigator, unsuitable for the study
• On more than 1 mg/kg/day prednisone or prednisone equivalent
• History of non-compliance
• History or other evidence of uncontrolled psychiatric illness that that would limit compliance with study requirements
• Receipt of an investigational agent within 28 days prior to screening
• Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of study enrollment, unless previously treated with curative intent (e.g. complete resected basal or squamous cell carcinoma of the skin)
• Active 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) or hepatitis C (defined as positive hepatitis C \[HCV\] antibody with positive HCV ribonucleic acid \[RNA\])
• Suspected active or latent tuberculosis (as confirmed by a positive QuantiFERON® test or other tuberculosis blood test)
• History of acute or chronic pancreatitis
• History of myositis
• Pregnant or breastfeeding
• Previous exposure to colony stimulating factor 1 receptor (CSF-1R) therapies

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

axatilimab; Specimen Handling

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Stephanie J. Lee, MD, MPH

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

cGVHD Intake Coordinator

CONTACT

206-667-4160; cgvhd@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 10, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): August 10, 2028
• Study Completion (Estimated): February 10, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)