A Phase 1/2 Study to Evaluate Axatilimab in Participants With Active cGVHD

NCT03604692 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SNDX-6352-0503
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 11

Brief Summary

This is a Phase 1/2, Open-label, Dose Escalation study to investigate axatilimab in participants with active chronic graft versus host disease (cGVHD).

Conditions

Chronic Graft-versus-host-disease

Keywords

cGVHD

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants With DLTs

  A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.

  Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1)

• Phase 1: Recommended Phase 2 Dose (RP2D)

  The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease \[cGVHD\] and pharmacokinetic/pharmacodynamic effects).

  Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1)

• Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168)

  CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.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. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.

  Cycle 7 Day 1 (Day 168)

Secondary Outcomes (15)

• Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352

  Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

• Phase 1: Observed Maximum Plasma Concentration for SNDX-6352

  Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

• Phase 1: Time to Observed Maximum Plasma Concentration

  Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

• Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations

  Baseline, Cycle 1 Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1 (28-day cycles), and end of treatment (EOT) (median duration of treatment = 7 months)

• Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++)

  Baseline, Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1, and EOT (median duration of treatment = 7 months)

Study Arms (2)

Cohorts of escalating dose levels of axatilimab

EXPERIMENTAL

Escalating dose levels of axatilimab to establish the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D). Intravenous (IV) infusion; axatilimab at a dose of 0.15 milligrams (mg)/kilogram (kg) to 3 mg/kg.

Drug: axatilimab

Phase 2 Dose Expansion

EXPERIMENTAL

Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample size. IV infusion; axatilimab at a dose of 1 mg/kg.

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

Cohorts of escalating dose levels of axatilimab; Phase 2 Dose Expansion

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 6 years of age or older, at the time of signing the informed consent.
• Participants who are allogeneic hematopoietic stem cell transplant (HSCT) recipients with cGVHD requiring systemic immune suppression.
• Participants with active cGVHD who have received at least 2 lines of therapy. Participants 18 or older with active cGVHD who have erythematous rash involving \>25% body surface area or a NIH mouth score of \>4 must have received prior ibrutinib therapy.
• a. 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 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 with a life expectancy of at least 3 months (if aged 16 years or older); Lansky Performance Score of ≥60 (if less than 16 years).
• Adequate organ and bone marrow functions.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent which includes compliance with the study requirements and restrictions.

You may not qualify if:

• 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 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.
• Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, unless previously treated with curative intent and must be approved by Sponsor 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 participants who are pregnant or breastfeeding.
• Previous exposure to study intervention or known allergy/sensitivity to study intervention.
• Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for treatment of cGVHD (This does not include agents being prescribed expressly for the treatment of acute GVHD).
• Receiving an investigational treatment within 28 days of study entry.

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37212-3505, United States

Location

University of Utah Health Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Kitko CL, Arora M, DeFilipp Z, Zaid MA, Di Stasi A, Radojcic V, Betts CB, Coussens LM, Meyers ML, Qamoos H, Ordentlich P, Kumar V, Quaranto C, Schmitt A, Gu Y, Blazar BR, Wang TP, Salhotra A, Pusic I, Jagasia M, Lee SJ. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. J Clin Oncol. 2023 Apr 1;41(10):1864-1875. doi: 10.1200/JCO.22.00958. Epub 2022 Dec 2.

  PMID: 36459673 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

axatilimab

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

Results Point of Contact

• Title: Syndax Pharmaceuticals
• 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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The dose-escalation phase is a sequential group (dose-escalating) treatment study that is open-label. The dose-expansion phase is a parallel group treatment study with open-label cohorts.

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 27, 2018
• Study Start: November 1, 2018
• Primary Completion: August 12, 2022
• Study Completion: October 18, 2024
• Last Updated: September 15, 2025
• Results First Posted: November 27, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)