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)

A Phase 2, Randomized, Open-Label Study of 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)

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.

Inclusion Criteria:

• Aged 2 to < 18 years at the time of randomization.
• 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, ibrutinib, or pentostatin.
• 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, including autologous CAR T-cell therapy given before the allo-SCT.
• Documented evidence of relapse of the primary hematologic disease or receipt of treatment for relapse after allo-SCT, including DLI for treatment of any malignancy relapse, including molecular relapse. Autologous and allogeneic donor-derived CAR T-cell therapy after allo-SCT are not allowed. Note: Participants who received DLI solely for the management of mixed chimerism or as part of the planned transplant procedure and not for treatment of malignancy relapse (including molecular 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 or ALT > 3 × ULN or 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.