• In preliminary results from a Phase I study of CLBR001 + SWI019 for patients with B cell malignancies: 7 of 9 patients responded and 6 of 9 had a complete response (78% ORR, 67% CR)
• CLBR001 cells engrafted at higher levels than approved CAR-T cell products without causing an increase in the incidence of CRS or ICANS
• Adjusting switch (SWI019) dosage shortened the duration of CRS and ICANS events and lowered incidence of Grade ≥ 3 ICANS compared to approved products
• Strong preliminary responses, high cell engraftment, and favorable safety profile of the sCAR-T cell platform highlight potential for universal application across a wide range of malignancies, including solid tumors

Calibr, a division of Scripps Research focused on the “bench to bedside” development of transformative medicines, today announced encouraging preliminary data from the first nine subjects in a first-in-human Phase 1 clinical trial studying the first switchable CAR-T cell product (CLBR001 + SWI019) for patients with B cell malignancies. The ongoing dose escalation trial investigating the safety, tolerability, and optimal dosing for Calibr’s next-generation “switchable” chimeric antigen receptor T-cell (sCAR-T) therapy platform is the first step towards development of a universal, more versatile, and safer approach to cell therapy.

The results, presented at Wednesday’s plenary session of the CAR-TCR Summit 2022, showed that CLBR001 + SWI019 achieved an overall response rate (ORR) of 78% (7 of the first 9 evaluable patients) and a complete response (CR) of 67% (6 of 9 patients) as of the data cut-off of July 22, 2022. Subjects participating in the study were heavily pretreated with a median of 5 prior therapies, including a subject who previously received NK cell therapy. Most responses were achieved with just a single dose of CLBR001 cells and one cycle of SWI019—with further cycles of SWI019 showing evidence of deepening responses over time.

Administration of CLBR001 + SWI019 was reported as generally well tolerated as of the data cut-off. No safety signals related to the cell product CLBR001 alone were reported, and clinical activity of the CLBR001 cells was, as designed, only observed following administration of the switch molecule SWI019. Patients who experienced CRS or ICANS had shorter duration of these events compared with those in pivotal trials for commercial CAR-T cell products (2­­­–3 days vs 5–17 days, respectively). This improvement in resolution of adverse events is attributable to the ability to hold or reduce the dose of SWI019 following CRS or ICANS, and effectively turn “off” the CLBR001 cells. The ability for the switch to control cell activity is foundational to the platform and supports the safety of the system.

Many of these promising early results were achieved in the lower dosing cohorts planned in the trial: starting at 140e6 CAR+ CLBR001 cells and just 10 μg/kg of SWI019. In the doses tested, CLBR001 cells reached higher levels in peripheral blood over the first 90 days compared with some commercial CAR-T cell products. Future cohorts will test higher doses of both CLBR001 and SWI019. The strong preliminary responses, robust engraftment, and shorter duration of adverse events differentiate the switchable platform from previous approaches. 

“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’,” said Travis Young, PhD, vice president of biologics at Calibr. “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 Phase 1 trial investigating CLBR001 + SWI019 is ongoing in dose escalation. No DLTs have been observed as of the data cutoff.

The sCAR-T platform technology was developed by Calibr, a division of Scripps Research, and a partnership with AbbVie has enabled this first-in-human trial. Expansion of the platform into solid tumors is currently underway.