“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.
Phase 1/2 Dibotatug Analysis in Cytotoxic T/Nk Cell Lymphomas: Highlights
- Dibotatug had a tolerable safety profile in patients with relapsed/refractory cytotoxic T/NK cell lymphomas, with IRRs being the most common but manageable TRAE.
- The therapy yielded durable efficacy across various histologic subgroups, notably reaching an 86% ORR in patients with SPTCL and a median duration of response of 10.6 months in the overall population.
- As a first-in-human antibody targeting the CD94 protein, dibotatug works by depleting malignant cells via antibody-dependent cellular cytotoxicity in rare disease subtypes that currently lack established treatment options.
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
- 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.
- 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
