Frontline Itolizumab Shows Durable Response Against aGVHD

Corey Cutler, MD, MPH, FRCPC

Updated results from the EQUATE study revealed that frontline itolizumab (Alzumab) had a rapid and durable response in patients with high-risk acute graft-versus-host disease (aGVHD). Corey Cutler, MD, MPH, FRCPC, of the Dana-Farber Cancer Institute presented these findings at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT).

Itolizumab showed high rates of clinical response. Specifically, at day 15, the overall response rate (ORR) was 71%. At day 29, complete response (CR) was 52% and ORR was 64% across all treatment doses. The highest day 29 CR of 61% was achieved in patients receiving itolizumab within 72 hours of also starting systemic corticosteroids

The EQUATE study (NCT03763318) is a phase 1b, open label, 3 + 3, dose escalation study.Investigators administered 3 doses with a cohort expansion after the dose escalation stage. A total of 25 patients with grades 3 to 4 GVHD were randomized to receive itolizumab in 5 biweekly, intravenous (IV) doses of 1.6 mg/kg (n = 9), 0.8 mg/kg (n = 12), or 0.4 mg/kg (n = 4). Itolizumab was administered on days 1, 15, 29, 43, and 57. Patients were monitored through day 337. The primary objectives of the study were to monitor the safety of IV itolizumab and to identify the optimal dose. Secondary objectives included characterizing the pharmacokinetics and pharmacodynamics of itolizumab as well as assessing ORR, non-relapse mortality, chronic GVHD, and durability.

Across all dose variations, 79% of day 29 responders maintained a response through day 169, and 55% through day 337. “It's important to note that 4 responders died while on study, two of whom died more than 6 months after initiating itolizumab,” said Cutler, medical director for the adult stem cell transplantation program and director of clinical research for stem cell transplantation at Dana-Farber.

Cutler continued, “We see that looking only at responders, progression-free survival was approximately 50% at 1 year. Looking at overall survival, stratifying by response or lack thereof at day 29, we note an extraordinarily high overall survival for subjects who did have early responses with over 75% [of patients] alive at 12 months.”

Itolizumab was also associated with dose reduction in patients who underwent systemic steroid use. The median steroid dose reduction for responders was 73% at day 29 and 96% at day 169.

The median age of patients was 55 years, and 64% were male. Sixteen patients had grade 3 aGVHD (64%), eight had grade 2 (32%), and 1 patient had grade 2 (4%). Ninety-six percent of patients had an Ann Arbor score of 2 or 3.

In the entire patient population, 16 patients experienced severe adverse events (AE), although 2 of these were considered related to the study intervention. There were 8 AEs that led to death, and 6 subjects had AEs that led to study drug discontinuation, including 3 that were related to infections. “There was 1 dose-limiting toxicity at the 1.6 mg/kg dose, which led to the expansion of the 0.8 mg/kg dose cohort,” Cutler commented.

These results were favorable enough to initiate a phase 3 study (NCT05263999), which will test itolizumab for the frontline treatment of aGVHD.

_REFERENCE

_{Cutler C. Updated interim results from the equate study: preliminary safety and efficacy of itolizumab, a novel targeted anti-cd6 therapy, in newly diagnosed acute graft-versus-host disease. Presented at the Virtual 48th Annual Meeting of the EBMT; March 19-23, 2022. Oral session 10: GVHD I, clinical}