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

Syndax Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Chronic Graft-versus-host-disease

Treatments: Drug: axatilimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03604692

SNDX-6352-0503

Details and patient eligibility

About

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

Full description

This is a dose escalation and dose expansion study in participants with active cGVHD who have received at least 2 lines of prior therapy.

Enrollment: 41 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Participant must be 6 years of age or older, at the time of signing the informed consent.

2. Participants who are allogeneic hematopoietic stem cell transplant (HSCT) recipients with cGVHD requiring systemic immune suppression.

3. 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.

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 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).

6. Adequate organ and bone marrow functions.

7. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

8. Capable of giving signed informed consent which includes compliance with the study requirements and restrictions.

Key Exclusion Criteria:

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 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.
4. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
5. 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).
6. Female participants who are pregnant or breastfeeding.
7. Previous exposure to study intervention or known allergy/sensitivity to study intervention.
8. 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).
9. Receiving an investigational treatment within 28 days of study entry.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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41 participants in 2 patient groups

Cohorts of escalating dose levels of axatilimab

Experimental group

Description:

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.

Treatment:

Drug: axatilimab

Phase 2 Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: axatilimab