Dibotatug Is Safe and Shows Activity in R/R Cytotoxic T/NK Cell Lymphomas

Dibotatug (DR-01) elicited tolerable safety and durable efficacy outcomes in patients with relapsed/refractory cytotoxic T- or natural killer (NK)–cell lymphomas, according to updated data from a phase 1/2 trial (NCT05475925) presented at the 6th World Congress on Cutaneous Lymphomas.¹

Among safety-evaluable patients (n = 114), infusion-related reactions (IRRs) were the most common treatment-related adverse effect (TRAE; 30%); most of these events were grade 1/2, and all events were manageable through mitigation strategies, such as standard premedications, as well as splitting the initial dose over 2 days. Other TRAEs included pyrexia (7%), anemia (7%), diarrhea (5%), headache (1%), nausea (2%), decreased lymphocyte counts (6%), and hypokalemia (2%). No treatment-related deaths occurred.

Overall, the most common treatment-emergent AEs were IRRs (30%), pyrexia (19%), fatigue (18%), anemia (18%), diarrhea (12%), headache (12%), nausea (10%), decreased lymphocyte counts (10%), and hypokalemia (10%).

Regarding efficacy, the overall response rates (ORRs) across histologic subgroups were as follows:

• Primary cutaneous gamma-delta T-cell lymphoma (PCγδTCL): 45% (complete response [CR], 15%; partial response [PR], 31%)
• Peripheral T-cell lymphoma not otherwise specified: 15% (8%; 8%)
• Subcutaneous panniculitis-like T-cell lymphoma (SPTCL): 86% (57%; 29%)
• Extranodal natural killer/T-cell lymphoma (ENKTL): 52% (39%; 13%)
• Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL): 40% (30%; 10%)
• Primary cutaneous aggressive epidermotropic CT8-positive T-cell lymphoma: 29% (14%; 14%)
• Hepatosplenic T-cell lymphoma: 44% (22%; 22%)

In the overall population, the median duration of response was 10.6 months, and the longest time on treatment was 34+ months and ongoing.

“One thing that was noted in the correlative [study] is that…the CD94 expression across all the categories is uniform,” Swaminathan P. Iyer, MD, stated in a presentation of the data. “There was no correlation between the expression and the responses. There’s still a lot to be learned here.”

Iyer is a professor of lymphoma/myeloma at The University of Texas MD Anderson Cancer Center in Houston.

What was the rationale for investigating dibotatug in cytotoxic T/NK cell lymphomas?

Cytotoxic T/NK cell lymphomas comprise a rare disease subtype that is characterized by cytotoxic cells expressing CD94. Currently, patients with relapsed/refractory disease have no established treatment options and poor outcomes.

Dibotatug is a non-fucosylated human IgG antibody that targets CD94, a protein that is expressed on terminal effector CD8-positive T cells, γδ T cells, and NK cells. Dibotatug depletes CD94-expressing malignant cells via antibody-dependent cellular cytotoxicity.

What was the design of the phase 1/2 trial of dibotatug in cytotoxic T/NK cell lymphomas?

This first-in-human, open-label, dose-escalation/extension and optimization trial enrolled patients with relapsed/refractory cutaneous T-cell lymphomas. Patients needed to have adequate organ function and an ECOG performance status of 0 or 1. In part A, patients needed to have received at least 2 prior lines of therapy; in part B, this requirement was at least 1 prior line.

In the dose-escalation portion, patients received intravenous dibotatug at doses ranging from 0.3 mg/kg to 10 mg/kg. The induction regimen for the part B expansion portion was administered on cycle 1 days 1, 8, and 15; after induction, patients received a maintenance dose every 28 days. Notably, the part B dose-optimization portion is ongoing.

“One of the key aspects of each patient who came on the study is that the majority of them did not have any response to the last therapy that they received,” Iyer noted.

In part A, the primary end points are safety and tolerability, as well as pharmacokinetics and pharmacodynamics.² In part B, the primary end point is ORR.

What case studies exemplify the efficacy of dibotatug in cytotoxic T/NK cell lymphomas?

Iyer highlighted a case study of a 19-year-old male patient with SPTCL who had received 4 prior lines of therapy, including corticosteroids, cyclosporine, methotrexate, and romidepsin.¹ This patient achieved a PR after the first cycle of dibotatug, which deepened to a CR after 5 cycles. After 14 study treatment cycles, this patient underwent allogeneic hematopoietic stem cell transplant and remained in remission for an additional 23+ months after.

Another case study that was highlighted was one of a 55-year-old male patient with SPTCL who initially presented in 2019 with subcutaneous nodules. This patient began dibotatug treatment in October 2025 and had a baseline mSWAT of 71. They achieved an initial response of PR at cycle 2 and then achieved a CR at cycle 4. This patient remained on study in CR at cycle 7.

The third case study involved a 75-year-old male patient who was initially diagnosed in 2021 with T2BN0M0 with PCγδTCL and had been previously treated with pralatrexate. This patient began treatment with dibotatug with a baseline mSWAT of 90 and had an initial response of stable disease at cycle 2, then achieved a PR at cycle 6. The patient remained on the study in a durable PR at cycle 13, and their last mSWAT was a 4.

The final case study that was presented was of a 69-year-old female patient with ENKTL who initially presented in 2023 with skin lesions in multiple regions. This patient was initially treated with gemcitabine, oxaliplatin, and l-asparaginase and concurrent radiation therapy. They started dibotatug treatment with a fungating mass on their right knee and achieved a PR at cycle 2 followed by a CR at cycle 4. This patient remained on study in a CR at cycle 9.

“[This is an] ongoing phase 2 study that continues to enroll globally and collaboration with the FDA,” Iyer concluded. “We hopefully will see the drug reach a lot more patients.”

References

1. Poh C, Zain J, Querfeld C, et al. Updated clinical data from the phase 1 study of dibotatug (DR-01), a non-fucosylated anti-CD94 Antibody in patients with relapsed/refractory cytotoxic T/NK cell lymphomas. Presented at: 6th World Congress on Cutaneous Lymphomas; June 25-27, 2026; Montreal, Quebec, Canada. Abstract 6.04.
2. A study of DR-01 in subjects with large granular lymphocytic leukemia or cytotoxic lymphomas. ClinicalTrials.gov. Updated June 17, 2026. Accessed June 26, 2026. https://clinicaltrials.gov/study/NCT05475925