A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

Incyte

Status and phase: Enrolling; Phase 2

Conditions: Chronic Graft-versus-host-disease

Treatments: Drug: Axatilimab; Drug: Corticosteroids; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06388564

INCA34176-254

2022-502168-19-00 (Registry Identifier)

Details and patient eligibility

About

This study will be conducted to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.

Enrollment: 120 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 12 years of age at the time of informed consent.
• New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
• History of 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells).
• Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC ≥ 0.75 × 109/L and platelet count ≥ 20 × 109/L.
• Willingness to avoid pregnancy or fathering children.

Exclusion criteria

• Received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
• Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
• Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
• Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication.
• Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
• Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity.
• Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse.
• History of acute or chronic pancreatitis.
• History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry.
• Active symptomatic myositis.
• Severe renal impairment, that is, estimated CrCl < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible.
• Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
• Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization.
• Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Treatment Group A

Experimental group

Description:

Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose.

Treatment:

Drug: Ruxolitinib

Drug: Axatilimab

Treatment Group B

Experimental group

Description:

Ruxolitinib will be administered at a protocol defined starting dose.

Treatment:

Drug: Ruxolitinib

Treatment Group C

Experimental group

Description:

Corticosteroids alone will be administered at a protocol defined starting dose.

Treatment:

Drug: Corticosteroids