Inside AGAVE-201: Axatilimab for Steroid-Refractory cGVHD

EP: 1.Understanding cGVHD: From Diagnosis to Initial Therapies

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EP: 2.Inside AGAVE-201: Axatilimab for Steroid-Refractory cGVHD

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Axatilimab is a fully humanized IgG4 monoclonal antibody that binds to the CSF-1 receptor expressed on monocytes and macrophages, particularly targeting nonclassical monocytes (characterized by high CD16 expression) that are increased in patients with chronic graft-vs-host disease (cGVHD). These monocytes migrate to target organs, becoming activated M2 macrophages that secrete inflammatory cytokines, especially transforming growth factor beta (TGF-β), promoting fibrosis. Preclinical studies demonstrated that axatilimab reduces circulating nonclassical monocytes, decreases macrophage infiltration in skin biopsies, and reduces TGF-β secretion in responders.

The AGAVE-201 trial was a large multicenter, international phase 2 study testing 3 different axatilimab dosing regimens in approximately 250 patients with cGVHD who had failed 2 prior lines of treatment. The 3 arms evaluated were: 0.3 mg/kg every 2 weeks, 1 mg/kg every 2 weeks, and 3 mg/kg every 4 weeks, all administered as 30-minute intravenous infusions. The primary end point was best overall response rate within the first 6 cycles of treatment, with assessments performed monthly using National Institutes of Health criteria. Secondary end points included duration of response, failure-free survival, and improvement in Lee symptom scores, with a 7-point reduction considered clinically significant.

Based on efficacy and safety data, the FDA selected the 0.3 mg/kg every 2 weeks dosing regimen for approval. The median duration of response was impressive, with 60% of patients remaining on study at the 1-year mark and failure-free survival reaching approximately 17 months. The responses were not only deep and durable but also occurred rapidly, with both objective response and symptom improvement occurring at a median of 1.5 months after treatment initiation. Approximately 56% of patients in the 0.3 mg/kg arm achieved the clinically significant 7-point reduction in Lee symptom scores, demonstrating meaningful improvement in quality of life.