Dibotatug (DR-01) produced durable responses and was well tolerated across dose levels in patients with large granular lymphocytic leukemia (LGLL), according to updated data from a phase 1/2 study (NCT05475925) presented at the 2026 SOHO Annual Meeting.¹
Among 45 evaluable patients treated at the 1-mg/kg (n = 22) or 6-mg/kg (n = 23) dose levels who reached the first response assessment, the overall response rate (ORR) was 60%, including a complete response (CR) rate of 40%. Of the 101 patients evaluable for safety, 91 received the selected induction regimen, and 73% remained on study treatment at a data cutoff of May 3, 2026, with time on treatment ranging from 0.2 months to more than 30 months. No treatment-related deaths or dose-limiting toxicities were observed across doses tested up to 10 mg/kg.
What is dibotatug, and how does it work in LGLL?
LGLL is a rare chronic lymphoproliferative disorder driven by clonal expansion of CD94-expressing cytotoxic CD8-positive T cells or natural killer (NK) cells, with prominent clinical features, including severe neutropenia, recurrent infections, symptomatic anemia, and transfusion dependence. The disease is frequently associated with autoimmune conditions, such as rheumatoid arthritis. Although many patients require treatment, no targeted therapies are approved, and the standard of care relies on immunosuppressants, including methotrexate, cyclophosphamide, and cyclosporine.
Dibotatug is a nonfucosylated IgG antibody targeting CD94, which is selectively expressed on cytotoxic lymphocytes, such as terminal effector CD8-positive T cells, γδ T cells, and NK cells. By engaging Fc-γ receptors like CD16a, dibotatug triggers antibody-dependent cellular cytotoxicity by effector cells, which rapidly depletes CD94-expressing target cells.
What was the design of the LGLL cohort of the phase 1/2 trial of dibotatug?
This open-label trial included a dose-escalation and extension phase testing dibotatug at doses of 0.3 mg/kg to 10 mg/kg intravenously. Eligible patients had T- or NK-cell LGLL that was either treatment naive or relapsed/refractory after at least 1 prior line of therapy. The selected induction regimen for part B was dosing on cycle 1 days 1, 8, and 15, followed by maintenance dosing every 28 days, with efficacy assessed using ECOG E5998 response criteria.
Dibotatug in LGLL: Key Takeaways
- Among evaluable patients treated at 1 mg/kg or 6 mg/kg, dibotatug produced a 60% ORR, including a 40% CR rate, in patients with LGLL.
- Responders experienced durable normalization of hemoglobin levels, neutrophil counts, and large granular lymphocyte counts, with the longest ongoing CR exceeding 27 months.
- No treatment-related deaths or dose-limiting toxicities occurred across all dose levels. IRRs were the most common TRAEs and were manageable with standard mitigation.
Among the 101 treated patients across all dose levels, the median age was 66 years (range, 24-87), 57% were male, 94% had T-LGLL, 6% had NK-LGLL, and 89% had relapsed/refractory disease. The most common primary indications for treatment were severe neutropenia (42%) and transfusion-dependent anemia (33%). Among relapsed/refractory patients, most had received prior methotrexate (84%), and 49% had received prior cyclophosphamide.
What response rates were observed with dibotatug in LGLL at the 1-mg/kg and 6-mg/kg dose levels?
Among the 45 evaluable patients who received dibotatug and reached the cycle 4 day 1 response assessment, the ORRs were similar between the 1-mg/kg and 6-mg/kg dose populations, at 59% and 61%, respectively, with CR rates of 36% and 43%, respectively. CRs were observed in patients whose primary treatment indications were either neutropenia or anemia. CRs occurred in both patients with T-LGLL and those with NK-LGLL.
The times to first response (CR or partial response) ranged from 0.9 months to 5.5 months, and the longest ongoing response was a CR lasting more than 27 months. Among responders, hemoglobin levels and absolute neutrophil counts rose, regardless of whether the primary treatment indication was for amenia or neutropenia. In patients achieving CR, large granular lymphocyte counts dropped rapidly, and these decreased counts were sustained during the study.
Many patients with stable disease remained on dibotatug for clinical benefit, including improved fatigue and reduced transfusion requirements. At the data cutoff, 32 additional patients, including 10 who were treatment naive, had not yet reached the first response assessment.
What was the safety profile of dibotatug in LGLL?
The most common treatment-emergent adverse effects (TRAEs) occurring in at least 10% of patients included headache and fatigue (20% each), nausea (19%), diarrhea (18%), infusion-related reactions (IRRs; 17%), anemia (14%), and pyrexia (13%). IRRs were the most frequently observed TRAEs, occurring mostly with the first dose and largely grade 1/2. No IRRs led to dose reduction or discontinuation except in the first enrolled patient, who was treated before IRR prophylaxis was optimized.
The investigators concluded that dibotatug was safe and well tolerated across dose levels in both relapsed/refractory and treatment-naive LGLL, and that responses were durable with rapid onset. The study remains ongoing and enrolling globally, including treatment-naive patients.2
References
- Kadia TM, Marchi E, Nakamura R, et al. Updated clinical data from the phase 1 study of dibotatug (DR-01), a nonfucosylated anti-CD94 antibody, in patients with large granular lymphocytic leukemia. Presented at: 2026 SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract TCL-418.
- A study of DR-01 in subjects with large granular lymphocytic leukemia or cytotoxic lymphomas. ClinicalTrials.gov. Updated June 17, 2026. Accessed September 11, 2026. https://clinicaltrials.gov/study/NCT05475925
