Interim data showed a 78% overall response rate and a 67% complete response rate.
Calibr’s CLBR001 + SWI019, an investigational combination immunotherapy, has demonstrated promising safety and efficacy in preliminary data from a phase 1 clinical trial (NCT04450069) in patients with relapsed/refractory (r/r) B-cell malignancies presented at the 7th Annual CAR-TCR Summit, in Boston, Massachusetts, on September 20-22.
CLBR001 is an autologous switchable chimeric antigen receptor (sCAR) T-cell product and SWI019 is an anti-CD19 antibody which acts as an adapter molecule to activate CLBR001 cells. The treatment yielded an overall response rate (ORR) of 78% (n = 7) and a complete response (CR) rate of 67% (n = 6) in the 9 patients who were evaluable as of the July 22, 2022, data cut-off date. Furthermore, it was generally well-tolerated and no dose-limiting toxicities (DLTs) were reported.
“These results underscore the potential of Calibr’s switchable CAR-T cell platform to act like a ‘software’ and ‘hardware’ approach, where the biological response of the CLBR001 cell ‘hardware’ can be programmed using the switch dose as the ‘software’,” Travis Young, PhD, vice president of biologics, Calibr, said in a statement. “This is our first step toward demonstrating the potential of this universal platform to be programmed toward any target, including those for solid tumors.”
The participants in the clinical trial were heavily pretreated with multiple prior therapies (median, 5), which in 1 patient included a natural killer(NK) cell therapy. The majority of responses were attained after a single dose of CLBR001 cells and a single cycle of SWI019, and additional SWI019 cycles revealed indications of a deepening response over time. Clinical activity of the CLBR001 cells was observed only after administration of SWI019, indicating that the switch activation was functioning as intended, and no safety signals related to CLBR001 alone were reported. Cases of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) had a shorter duration (2-3 days) than cases seen in pivotal trials of commercial CAR-T products (5-17days), which was attributed to the ability to deactivate the CLBR001 cells by withholding or reducing additional administrations of SWI019. There was also a lower incidence of grade 3 or higher ICANS compared to approved CAR-T therapies.
The on-going, open-label, multicenter clinical trial, being conducted in collaboration with AbbVie, is enrolling approximately 36 patients aged 18 years or older with r/r B-cell malignancies. Participants are required to have received at least 2 lines of adequate prior therapy, must be ineligible for and have no history of allogeneic stem cell transplant, have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1, and a life expectancy of at least 12 weeks. Patients with certain disease histologies, including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance, and T-cell histiocyte large B-cell lymphoma will be excluded from the study. Additional exclusion criteria relate to patient health status and previously received treatments.
CLBR001 + SWI019 is being administered via infusion at ascending dose levels, starting with 140x106 CAR+ CLBR001 cells and 10 μg/kg of SWI019, with the intention of determining the maximum tolerated dose and/or the optimal SWI019 dose. The primary end points of the study are the number of first cycle DLTs and the frequency, relatedness, severity, and duration of treatment-emergent adverse events. Secondary end points include the maximum drug concentration, area under the curve, time to reach Cmax, clearance, and apparent elimination half-life of SWI019 in patients’ peripheral blood; the quantification of CLBR001 cells in the peripheral blood; and the phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies. Additional secondary end points include the immunogenic responses to CLBR001 and SWI019, serum cytokine concentrations, overall best objective response, duration of response, progression-free survival, and overall survival. The study is recruiting at locations throughout the United States and is estimated to be completed in April 2024.