Paper Details

ABSTRACT

Dibotatug (DR-01) is a non-fucosylated human IgG antibody targeting CD94 which is selectively expressed on NK cells and cytotoxic CD8+ T cells, and has shown promising safety and efficacy in cytotoxic T/NK cell lymphomas (CTL) and large granular lymphocytic leukemia (LGLL) (Iyer 2026, Kadia 2026).  Acquired aplastic anemia (AA) is the prototypical bone marrow failure (BMF) syndrome, defined by a hypocellular marrow and pancytopenia, and there remains a high unmet need in AA after failing immunosuppressive therapy (IST).  Analysis of data from clinical samples revealed that bone marrow samples from AA patients are enriched with cytotoxic CD8+ T cells expressing granzyme B and CD94 which provides the rationale for evaluating dibotatug in patients with AA and other BMF syndromes.

This Phase 1/2 open-label trial (NCT07712562) is evaluating the safety and efficacy of dibotatug in adult patients with bone marrow failure (BMF) syndromes. Participants will initially be enrolled in the following cohorts: refractory severe aplastic anemia (SAA) (Cohort A), relapsed SAA (Cohort B), and relapsed/refractory transfusion-dependent non-severe aplastic anemia (RR-TD-NSAA) (Cohort C). Stage 1 will evaluate the safety and preliminary efficacy in up to 12 evaluable participants.  If deemed appropriate by the Safety Review Committee based on review of initial safety and efficacy data of at least 12 participants in Stage 1, the study will transition into Stage 2, enrolling up to approximately 20 participants in each cohort for up to a total of up to 60 participants.

Primary objectives include evaluating the safety, tolerability, and efficacy of dibotatug in participants with BMF syndromes. Secondary objectives include evaluation of overall response rate (CR + PR) at 3 and 6 months, duration of response and time to response. Quality of life will be measured using the EORTC QLQ-C30 questionnaire.  Exploratory objectives include evaluation of CD94+ target cells in peripheral blood and bone marrow and serum cytokines.

Dibotatug will be administered intravenously as a split dose on Days 1 and 2, Day 8, Day 15, followed by every 4 weeks starting on Week 4. The main treatment period of this study is 24 weeks in duration.  Participants who achieve a complete response (CR) or partial response (PR) by Week 24 will have the option to continue dosing through Week 48.

Key eligibility criteria include participants age of 18 years or older. Participants with SAA (Cohorts A and B) must have a diagnosis of SAA or very severe AA and those with refractory SAA (Cohort A) must have received one ≥ 3-month course of antithymocyte globulin (ATG) and/or cyclosporine A (CSA)-based IST. Refractory SAA is defined as failure to achieve a response ≥ 3 months after starting ATG and/or CSA-based IST. For participants with relapsed SAA (Cohort B), relapsed SAA is defined as relapse following a response that was achieved ≥ 3 months after starting ATG- and/or CSA-based IST. Participants with RR-TD-NSAA (Cohort C) must have a diagnosis of NSAA, no current or prior diagnosis of SAA, received at least 1 prior course of IST such as ATG- or CSA, with or without a thrombopoietin receptor (TPO-R) agonist (lasting ≥3 months), and meets criteria for transfusion dependence (either RBC or platelets).

This multi-center trial will enroll participants at several sites across the United States.