A Study to Evaluate Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256)

Incyte

Status and phase: Enrolling; Phase 2

Conditions: Chronic Graft-versus-host-disease

Treatments: Drug: INCA034176; Drug: Best available Treatment (BAT)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07124078

INCA034176-256

Details and patient eligibility

About

This study will be conducted to compare Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy.

Enrollment: 60 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged ≥ 2 to < 18 years at the time of signing the informed consent.
• Active, moderate to severe cGVHD, requiring systemic immune suppression.
• Participants with refractory or recurrent cGVHD who have received at least 2 lines of systemic therapy, including corticosteroids and ruxolitinib.
• Concomitant use of systemic corticosteroids is allowed. Participants on systemic corticosteroids must be on a stable dose of corticosteroids for at least 2 weeks prior to C1D1. Topical and inhaled corticosteroid agents are allowed.
• Participants must accept to be treated with one of the following BAT options on C1D1: CNI (cyclosporine or tacrolimus), ECP, MMF, an mTOR inhibitor (everolimus or sirolimus), rituximab, imatinib, methotrexate, or ibrutinib.
• History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.

Exclusion criteria

• Receipt of more than 1 prior allo-HCT. Prior autologous HCT is allowed.
• Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
• Severe renal impairment, that is, GFR < 30 mL/min/1.73 m2 as estimated using modified Schwartz formula, or end-stage renal disease on dialysis.
• 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.
• History of acute or chronic pancreatitis.
• Active, symptomatic myositis.
• Female adolescent participants who are 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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60 participants in 2 patient groups

Axatilimab

Experimental group

Description:

Axatilimab at the protocol-defined dose.

Treatment:

Drug: INCA034176

Best available Treatment (BAT)

Experimental group

Description:

Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Treatment:

Drug: Best available Treatment (BAT)