Following positive data examining ABC008 for inclusion body myositis, a phase 1/2 trial has begun evaluating the agent in patients with T-cell large granular lymphocytic leukemia.
Trial Name: ABC008 in Subjects With T-cell Large Granular Lymphocytic Leukemia (T-LGLL)
ClinicalTrials.gov Identifier: NCT05532722
Sponsor: Abcuro, Inc.
Recruitment Contact: Michael McClain, 617-865-5078, LGL-101_ClinicalTrial@abcuro.com
Completion Date: December 2023
A phase 1/2 dose-escalation trial (NCT05532722) evaluating the safety, tolerability, and proof-of-concept of ABC008 in patients with T-cell large granular lymphocytic leukemia (T-LGLL) who suffer from anemia and/or neutropenia has been initiated, according to Abcuro, Inc.1
ABC008 is a first-in-class anti-KLRG1 antibody. The agent can selectively deplete highly cytotoxic T cells while also sparing regulatory T cells, central memory T cells, and other immune cells.
“Initiating the phase 1/2 clinical trial of ABC008 represents an important step toward a potential breakthrough in the treatment of T-LGLL,” said Jeffrey Wilkins, MD, chief medical officer of Abcuro, Inc, in the press release “This trial builds upon prior published data demonstrating the ability of ABC008 to deplete highly cytotoxic T cells, which attack and destroy muscle tissue in inclusion body myositis, an autoimmune disease.”
The open-label, ascending dose study will evaluate adult patients with T-LGLL across 4 dose levels, including 0.5 mg/kg, 1.0 mg / kg, 2.0 mg / kg, and 3.0 mg / kg.2
Patients at least 18 years of age with a body mass index of 35 kg/m2 or less with a documented diagnosis of T-LGLL are eligible for enrollment. Further, patients must have had any 1 or more of the following at screening: absolute neutrophil count (ANC) < 0.5 x 109/L, ANC ≥ 0.5 x 109/L and < 1.0 x 109/L associated with recurrent infection, Hgb < 8 g/dL or packed red blood cell transfusion frequency ≥ 1 time in the 4 weeks before screening, or Hgb ≥ 8 g/dL and <10 g/dL accompanied by documented symptoms of anemia. Further, patients must have adequate hepatic and renal function.
The primary end points are to assess the incidence, nature, and severity of treatment-emergent adverse events (AEs) and serious AEs. Secondary end points include change from baseline in safety lab regarding hematology, chemistry, coagulation, complement, cytokines, CMV viral load, and EBV viral load, change from baseline in ECG for rhythm, heart rate, and parameters, change from baseline in systolic and diastolic blood pressure, temperature, respiratory rate, and pulse rate.
Other secondary end points include overall response rate, complete response, partial response, duration of response, overall survival, change from baseline in levels of KLRG1 expressing lymphocytes, T-LGL counts, and lymphocyte subsets over time, maximum serum concentration, time to maximum concentration, the area under the concentration-time curve, the apparent clearance and volume of distribution of ABC008, and the elimination half-life.
With an estimated study completion date of December 2023, the trial has an estimated enrollment of 15 patients and is currently recruiting patients in Utah.
“The limited efficacy of current standard of care is reflected in an overall reduced life expectancy for T-LGLL patients,” added Paul Shami, MD, professor of medicine in the Division of Hematology and Hematologic Malignancies at the University of Utah and principal investigator of the study, in the press release. “Without any approved treatment options for T-LGLL, many patients turn to off-label therapies, such as methotrexate, a non-specific immunosuppressant, which often have limited effectiveness.”
