Dr Kadia on Efficacy and Safety of Dibotatug in LGLL

“We saw an overall response rate of [approximately] 60%, [including] complete and partial remissions in a population where we typically see response rates in the range of 40% with the single-agent drugs we’ve had previously.”

Tapan M. Kadia, MD, a professor of leukemia, director of the T-cell LPD and Aplastic Anemia Program, and co-leader of the Section of Developmental Therapeutics in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed updated data from a phase 1/2 trial (NCT05475925) evaluating the anti-CD94 antibody dibotatug (DR-01) in patients with large granular lymphocytic leukemia (LGLL).

Dibotatug is being given intravenously on days 1, 8, and 15 of cycle 1, followed by maintenance dosing every 28 days, Kadia explained. Since the agent is a monoclonal antibody, infusion-related reactions (IRRs) were expected and occurred in 17% of patients in the most recent readout, Kadia said. These were predominantly seen with the first dose. After an early, more significant IRR prompted premedication with steroids and a smaller dose on day 1 followed by a slightly larger dose on day 2, most patients tolerated subsequent dibotatug infusions without incident, according to Kadia. He noted that IRRs were mostly grade 2 or lower and that beyond the first dose, additional toxicity was observed less frequently; the most common residual adverse effects were headache and fatigue.

The trial has enrolled more than 100 patients with LGLL to date, Kadia said, most with previously treated T-LGLL and approximately 11 with newly diagnosed disease. Across 2 cohorts of evaluable patients who reached the first response assessment (n = 45), the overall response rate was approximately 60%, including a complete response (CR) rate of approximately 40%. Kadia noted that patients in the relapsed/refractory population had received a median of 2 prior therapies (range, 1-13), including methotrexate, cyclosporine, and cyclophosphamide, and that the criteria for CR were stringent, requiring an absolute neutrophil count of greater than 1500/µL, hemoglobin levels of at least 11 g/dL, and platelet counts of at least 100,000/µL.

These data compare favorably with the approximately 40% response rate historically seen with single-agent immunosuppressive therapies in this setting, Kadia said. He called the results a potentially dramatic advance for a disease long managed with nonspecific agents, such as cyclosporine, methotrexate, and cyclophosphamide, which he said are associated with greater long-term toxicity than what has been observed with dibotatug so far.