Exposure-Response Relationships for Axatilimab in Patients with Chronic Graft-Versus-Host Disease.

Axatilimab, a high-affinity humanized monoclonal antibody that targets colony-stimulating factor 1 receptor, is approved for the treatment of chronic graft-versus-host disease (cGVHD). Here, we describe the exposure-response relationships for efficacy and safety in patients with cGVHD who received axatilimab. Exposure-efficacy relationships were assessed in treated patients in the AGAVE-201 study (n = 239); exposure-safety relationships were assessed in treated patients in AGAVE-201 (n = 239) and the phase 1/2 SNDX-6352-0503 study (n = 39). For binary or time-to-event endpoints, logistic or Cox regression analyses, respectively, were performed using axatilimab exposure metrics that were derived from a previously developed population pharmacokinetic/pharmacodynamic model. Overall response and ≥ 7-point improvement in modified Lee Symptom Scale responses were associated with axatilimab exposure, with lower axatilimab exposure increasing the odds of a response. Duration of response was not associated with axatilimab exposure. Ten of 11 safety endpoints were associated with axatilimab exposure, with higher axatilimab exposure increasing the odds of adverse events. Among the 3 regimens evaluated in AGAVE-201, the 0.3 mg/kg once every 2 weeks (Q2W) regimen had the highest predicted probability of response. Additionally, this dose group had the lowest predicted probability of event occurrence across all 10 safety endpoints associated with exposure among the evaluated regimens. Despite body weight influencing axatilimab exposure by > 20%, its effect on efficacy and safety endpoints remained minimal, with a maximum difference of ≤ 0.4% and ≤ 4.4% between the 1st and 4th quartiles of body weight, respectively. Taken together, these findings support the benefit-risk profile of axatilimab 0.3 mg/kg Q2W in patients with cGVHD.