Safety and Efficacy of Axatilimab in Patients with Chronic Graft-Versus-Host Disease (AGAVE-201)

Introduction Chronic graft-versus-host disease (cGVHD), a major cause of morbidity for recipients of allogeneic hematopoietic stem cell transplantation, is driven by multiorgan inflammation and fibrosis. Colony-stimulating factor 1 receptor (CSF-1R)-dependent monocytes and macrophages play a key role in both pathways. Axatilimab (AXA) is an investigational, high-affinity anti–CSF-1R monoclonal antibody. Objectives AGAVE-201 (NCT04710576) is a pivotal, phase 2, open-label, randomized, multicenter study evaluating AXA at 3 dose levels in patients (pts) with recurrent/refractory cGVHD. This analysis focuses on the 0.3 mg/kg every 2 wk (Q2W) dose, which showed the highest responses and most favorable safety profile among the cohorts. Methods Eligible pts were randomized 1:1:1 to intravenous AXA (0.3 mg/kg Q2W; 1 mg/kg Q2W; 3 mg/kg every 4 wk) and continued based on investigator assessment of clinical benefit. The primary endpoint was overall response rate (ORR) by Cycle 7 (wk 24) per National Institutes of Health 2014 criteria. The key secondary endpoint was the proportion of pts with a ≥7-point decrease in modified Lee Symptom Scale score (mLSS). Other secondary endpoints included organ-specific responses, failure-free survival (FFS), and safety. Results Among 80 pts enrolled in the 0.3 mg/kg cohort (7 Apr 2023 cutoff), 79 were treated. The median time from cGVHD diagnosis was 3.9 y (range, 0.4–17.6), and median number of prior therapy lines was 4 (range, 2–12). The ORR (95% CI) by Cycle 7 was 73.8% (62.7–83.0) and were 78.9% (66.1–88.6), 81.5% (61.9–93.7), and 75.0% (47.6–92.7) among pts with prior exposure to ruxolitinib (n=57), ibrutinib (n=27), and belumosudil (n=16), respectively. Responses (complete and partial) were seen in all involved organs, including lungs (15/32; 46.9%), joints/fascia (42/55; 76.4%), and esophagus (18/23; 78.3%; Figure). A ≥7-point mLSS reduction was achieved by 55.1% of pts. Median FFS was 11.1 mo (95% CI, 7.9–not estimable). Common adverse events (AEs) are summarized in the Table; 6.3% of pts discontinued owing to AEs. Conclusion In AGAVE-201, the primary endpoint was met. AXA 0.3 mg/kg Q2W was well tolerated and resulted in robust clinical activity and durable responses.