Calibr Announces Preliminary Clinical Data from First-in-Human Clinical Trial of Switchable CAR-T Cells (CLBR001 + SWI019) in Lymphoma Patients at 63rd Annual ASH Meeting
Two of the first three patients in the lowest dose cohort experienced a complete response to therapy with the longest response being 11 months (ongoing) at the time of data cut-off
The novel switchable CAR-T therapy showed a favorable profile with no toxicities associated with the cell product (CLBR001) alone, validating the universal platform approach to cell therapy
La Jolla CA— Calibr, a division of Scripps Research focused on the “bench to bedside” development of transformative medicines, will present preliminary data on the development of a novel switchable CAR-T cell platform for patients with relapsed/refractory lymphoma and leukemia. Preclinical IND-enabling studies supporting the first-in-human clinical study will be presented on December 11 at 5:30 p.m. and the clinical data was presented on December 12, 2021. at the 63rd Annual ASH meeting.
CLBR001 + SWI019 is the first clinical demonstration of Calibr’s novel “switchable” CAR-T cell platform technology, in which the activity of a universal CAR-T cell product (CLBR001) is controlled through dosage of an antibody-based molecule targeting CD19 referred to as a “switch” (SWI019). The approach represents a paradigm shift from conventional CAR-T cell therapy in that the activity of the CAR-T cells can be switched on or off through dosing of the switch to the patient. This type of switchable control over the cells is expected to improve safety T cell durability of the therapy. Importantly, the CLBR001 switchable CAR-T is universal; by changing the switch, the CAR-T cells can be programmed to attack different antigen targets and thereby treat multiple cancers.
As of the data cutoff, 5 patients (2 with mantle cell lymphoma (MCL), 2 with follicular lymphoma (FL), and 1 with marginal zone lymphoma (MZL)) had been treated across two cohorts. Two of the first three patients who received the lowest doses of CLBR001 and SWI019 in cohort 1 of the dose escalation trial experienced a complete response to treatment as assessed by Lugano
criteria. Durability of the response appears promising, with the longestresponse ongoing at 11 months. Treatment in cohort 2 is ongoing.
In the preliminary safety and tolerability data for CLBR001 + SWI019, no adverse events related to the cell product CLBR001 alone were reported, validating the design of the universal cell product to be functionally “off” in the absence of SWI019. Following administration of the switch molecule SWI019, two subjects experienced transient cytokine release syndrome (CRS) of
severity grades 1 and 3. The subject who experienced Grade 1 CRS also experienced Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). These cases of CRS/ICANS resolved quickly with typical CRS treatment followed by holding or reducing SWI019 dose, supporting the ability to adjust the CAR-T response in real time.
“We are very excited by initial signs of activity even at the lowest doses of CLBR001 and SWI019,” says Travis Young, PhD, Calibr’s vice president of biologics and lead on the CAR-T development at Calibr. “We believe this underscores the potential of this therapy to not only benefit patients with blood cancers, but patients with solid tumors as well.”
Liana Nikolaenko, MD, from City of Hope is the lead author on the poster presentation. “Switchable CAR-T cell platform, as designed by Calibr, is a remarkable technology enabling a delivery of the targeted therapy for patients with relapsed or refractory B-cell malignancies with a unique approach to mitigate potential toxicities that could be associated with CAR-T cell treatment, which can be severe and life-threatening,” says Nikolaenko. “The preliminary results of this novel approach are encouraging.”
Calibr has partnered the switchable CAR-T cell platform with AbbVie and together they are collaborating on developing the switchable CAR-T cell platform for solid tumor indications. AbbVie holds certain rights to commercialization.