Phase 3 EQUATOR Study to Initiate Itolizumab Treatment in Patients With aGVHD

The phase 3 EQUATOR clinical trial has been initiated in the United States for the treatment of patients with acute graft-versus-host disease.

A phase 3 study (EQUATOR; NCT05263999) is investigating treatment with itolizumab (Alzumab) in patients with acute graft-versus-host disease (aGVHD), according to an announcement by Equillium, Inc.1

The randomized, double-blind study is set to assess the efficacy and safety of itolizumab, in combination with corticosteroids, versus placebo as a first-line therapy for aGVHD. The primary objective is to see if patients can achieve early disease response with secondary objectives including evaluating durability of response to treatment, corticosteroid use, survival outcomes, and chronic GVHD incidence.

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that targets the CD6-ALCAM pathway, which modulates the activity of T cells that drive immunoinflammatory diseases.

The primary end point of the assessment itself is to evaluate the patients’ complete response rate on Day 29 of treatment. Key secondary end points include the overall response rate (ORR) at day 29 and how durable the complete response rates are from day 29 through day 99.2

“Acute GVHD remains a potentially lethal condition," said John Koreth, MD, associate professor of Medicine, Harvard Medical School, in a press release.1 "With no drugs approved for the first-line treatment setting, clinicians are eager for therapeutic options beyond standard-of-care high-dose systemic corticosteroids. Itolizumab demonstrated impressive complete response rates in the EQUATE study that were both rapid and durable, and which compared favorably to historical data with corticosteroid therapy alone. If successful in the EQUATOR study, itolizumab could result in the first approval of a novel therapeutic in the first-line treatment of acute GVHD, potentially transformative in the field."

Previous results of the EQUATE study (NCT03763318) showed that at day 29 of treatment with itolizumab, 52% experienced a complete response with an ORR of 64% among 25 treated patients. Eighteen of the patients in this trial were given corticosteroid within the first 3 days of treatment and those patients had a complete response of 61% and an ORR of 67%. Moreover, responses were observed within 15 days and 79% of patients maintained their response at 6 months. This led to researchers looking at the use of corticosteroids and itolizumab together in the frontline.

The EQUATOR trial will look at 200 adult and adolescent patients with grade 3-4 aGVHD, or grade 2 aGVHD with lower gastrointestinal involvement. Patients will receive itolizumab within 3 days of the first administration of high-dose corticosteroids in a 1–99-day treatment period and then a follow up at days 100-365. Patients will be randomized 1:1 to either 1.6 mg/kg of itolizumab followed by 6 doses of 0.8 mg/kg once every 2 weeks plus systemic corticosteroids, or placebo with 7 doses given every 2 weeks plus systemic corticosteroids as well.2

To enroll, patients must been aged 12 or older and have undergone initial allogenic hematopoietic stem cell transplant, have evidenced of myeloid engraftment, and a clinical diagnosis of aGVHD grade IIII-IV or grade II with LGI involvement.

“The initiation of this pivotal study marks a major milestone for Equillium to assess itolizumab’s potential as a life-changing advancement for patients suffering from acute GVHD," said Bruce Steel, chief executive officer of Equillium, in the press release.1 "Patients who do not respond to existing standard of care – high-dose corticosteroids – have very poor outcomes with high mortality rates…. Hematologists and transplantation specialists have highlighted their enthusiasm for itolizumab as a potential therapeutic option and we are optimistic for these patients as we launch the EQUATOR study."

References

1. Equillium Announces Initiation of the Phase 3 EQUATOR Study of Itolizumab in First-line Acute Graft-Versus-Host Disease. News release. Equillium, Inc. March 4, 2022. Accessed: March 8, 2022. https://bit.ly/3MANweC

2. A study of itolizumab in combination with corticosteroids for the first-line treatment of acute graft versus host disease (EQUATOR). Clinicaltrials.gov Accessed March 8, 2022.https://bit.ly/3KhBoxf