A Phase 1b Study of Efmarodocokin Alfa, an Interleukin-22 Agonist, in Combination with Standard of Care, in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft-versus-host disease (aGVHD) remains a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT), and no nonimmunosuppressive pharmacologic therapies are currently available for prophylaxis. We conducted a Phase 1b, open-label, dose-escalation study to evaluate the safety, pharmacokinetics (PK), and preliminary activity of efmarodocokin alfa, an interleukin-22 agonist, administered with standard-of-care prophylaxis in patients undergoing matched unrelated and matched related donor allogeneic HSCT following myeloablative conditioning. Eighteen patients were enrolled across 3 dose cohorts receiving efmarodocokin alfa at 30 µg/kg every 4 weeks, 30 µg/kg every 2 weeks, or 60 µg/kg every 2 weeks. Efmarodocokin alfa was well-tolerated and demonstrated an acceptable safety and PK profile, characterized by predominantly Grades 1 to 2 adverse events and linear PK across all dose levels. All patients achieved neutrophil engraftment by Day 30. By Day 100 post-transplant, 5 patients (27.8%) developed Grade 2 aGVHD, 2 (11.1%) of which had Stage 1 lower GI aGVHD. No patients developed Grades 3 to 4 aGVHD. Exploratory analysis demonstrated a lower gastrointestinal aGVHD-free survival rate of 83.3% at Day 180 and overall survival of 77.8% at Day 365. Although conclusions regarding efficacy are limited by the small sample size and exploratory design, these results demonstrate favorable safety and PK characteristics and provide initial observations regarding the potential role of efmarodocokin alfa in the prevention of lower gastrointestinal aGVHD as a nonimmunosuppressive prophylactic strategy.