DR-01 is a non-fucosylated human IgG antibody targeting CD94, a receptor selectively expressed on cytotoxic terminal effector CD8+T cells, γδT cells, and NK cells, leading to rapid depletion of target cells primarily by antibody-dependent cellular cytotoxicity, including fratricide (cytotoxic lymphoma cells depleting each other).
DR-01-ONC-001 (NCT05475925) is a Phase 1/2 study of DR-01 in relapsed/refractory (RR) cytotoxic lymphomas (CTLs) driven by CD94-expressing cytotoxic cells of origin. RR CTLs have no established effective treatment options, with shortened survival of only weeks to months.
From July 2022 to October 2024, this study enrolled 40 CTL and 14 large granular lymphocyte leukemia (LGLL) patients who failed ≥2 and ≥1 prior lines of therapy, respectively. During Part A dose-escalation, patients received intravenous DR-01 (0.3-10 mg/kg) in one of three induction regimens followed by monthly dosing. In the safety population (n=40 CTL; n=14 LGLL), no dose-limiting toxicities occurred; the only significant treatment-related adverse event was infusion-related reaction (39%; n=21), mainly with first administration and well managed with standard mitigation measures. Possibly related serious AEs of pyrexia (n=1; grade 2) and possible cytokine release syndrome (n=1; grade 2) resolved without sequelae. In the Part A efficacy population (n=21 CTL), objective response rate was 33.3% (3 complete responses, 4 partial responses). Duration of response in these patients was 2-14.1 months. During dose-optimization (n=40 CTL), doses of ≥1 mg/kg and induction dosing on C1D1, D8, and D15 best achieved the response-associated Cmin.
DR-01's safety, tolerability, and encouraging response rate supports its potential as a viable CTL treatment option.
