Incyte, Syndax announce full results from pivotal Phase 2 AGAVE-201 trial

Incyte (INCY) and Syndax Pharmaceuticals (SNDX) announced the full results from the pivotal Phase 2 AGAVE-201 trial of axatilimab, an anti-CSF-1R antibody, in adult and pediatric patients with refractory chronic graft-versus-host disease who had received at least two prior lines of systemic therapy. These data are featured today in the Plenary Scientific Session at the 65th American Society of Hematology Annual Meeting 2023. The results, which build on previously announced topline data, show that the trial met the primary endpoint across all cohorts receiving axatilimab, at doses of 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks and 3.0 mg/kg every four weeks. Patients who received axatilimab at 0.3 mg/kg every two weeks achieved the highest overall response rate of 74% within the first six months of treatment. Patients in this cohort experienced a median time to response to axatilimab of 1.7 months, and 60% of patients maintained a response at 12 months. The recommended dose of axatilimab for future trials in chronic GVHD is 0.3 mg/kg every two weeks. The AGAVE-201 trial also met key secondary endpoints in the 0.3 mg/kg dose, with 55% of patients achieving a greater than or equal to 7-point improvement in the modified Lee Symptom Scale score. Organ-specific responses, including complete responses, were seen across all organs involved at baseline, including lower gastrointestinal, upper GI, esophagus, joints/fascia, mouth, lungs, liver, eyes and skin. Additionally, responses were notable in fibrosis-dominated organs, including the esophagus, joints and fascia, lungs and skin. The AGAVE-201 pivotal trial enrolled 241 patients with relapsed and refractory cGVHD who had received two or more prior systemic therapies, with 74% having previously received ruxolitinib, 31% having previously received ibrutinib and 23% having previously received belumosudil. Patients were enrolled across 121 sites in 16 countries. The most common treatment-emergent adverse events were consistent with the on-target effects of CSF-1R inhibition and with what was previously observed with axatilimab treatment. In the overall trial population, 33% of patients experienced at least one grade greater than or equal to 3 TEAE, with 15.5% experiencing adverse events leading to discontinuation of treatment. For patients who received axatilimab at 0.3 mg/kg, grade greater than or equal to3 TEAEs occurred in 17.7% of patients, with 6.3% experiencing TEAEs leading to discontinuation of treatment. Based on these results and pending agreement from the U.S. Food and Drug Administration, Syndax and Incyte expect to submit a Biologics License Application to the FDA by year-end 2023.