Positive interim results of the EQUATE study—Itolizumab for acute graft-versus-host disease

On August 10, 2020, interim data from the initial two cohorts of the phase Ib, open-label, dose-escalation portion of the EQUATE study were announced. The results suggest that the first-in-class anti-CD6 monoclonal antibody, itolizumab, is well tolerated in patients with acute graft-versus-host disease (aGvHD) and demonstrates promising clinical efficacy in this setting.¹

EQUATE (NCT03763318)¹

The phase Ib/II EQUATE study is evaluating the safety, pharmacokinetic/dynamic, and efficacy profiles of itolizumab for the treatment of severe aGvHD (Grades 3 and 4). Itolizumab is under investigation as a first-line treatment alongside standard of care.

Itolizumab²

Itolizumab exerts its clinical activity by interrupting the CD6–ALCAM pathway, which is integral in the activation and trafficking of T cells that drive several immune-inflammatory conditions, including aGvHD. Itolizumab binds to the scavenger receptor cysteine-rich distal domain 1 of CD6, making it highly selective for the CD6–ALCAM pathway.

Results¹

Itolizumab demonstrated promising patient response rates (Table 1), and any adverse events reported were typical of those observed in the severe aGvHD setting. Data from these first two patient cohorts have supported a further dose escalation (1.6 mg/kg) of itolizumab in a third cohort of the EQUATE study.

Table 1. Patient outcomes to itolizumab in the dose escalation potion of the EQUATE trial¹

CR, complete response; CRR, complete response rate; OR, overall response; ORR, overall response rate * One patient in Cohort 1 was discontinued and replaced following aGvHD progression. One patient in Cohort 1 experienced a mild/moderate infusion-related reaction.
Cohort	Itolizumab dose, mg/kg	Number of Patients	CR, n	CRR, % All/evaluable (receiving ≥ 2 doses)	OR, n	ORR, % All/evaluable (receiving ≥ 2 doses)
1	0.4	4*	2	50/66	2	50/66
2	0.8	3	3	100/100	3	100/100
1 & 2	See above	7	5	71/83	5	71/83

Additional information

A request for a Pre-Investigational New Drug meeting has been submitted to the U.S. Food and Drug Administration (FDA) to discuss the potential of a global randomized, controlled clinical trial to evaluate itolizumab for the treatment of hospitalized patients with COVID-19.