Allogeneic CAR T Fast Tracked for R/R Multiple Myeloma

The FAD has granted Fast Track designation to Caribou Biosciences’ allogeneic chimeric antigen receptor (CAR) T-cell therapy CB-011 for the potential treatment of relapsed or refractory multiple myeloma (r/r MM).¹

“Fast Track designation for CB-011 allows us instrumental interactions with the FDA as we progress our clinical development and regulatory plans for CB-011. This designation could not be more timely as we recently dosed our first patient in the CaMMouflage Phase 1 trial,” Syed Rizvi, MD, chief medical officer, Caribou, said in a statement.¹ “Our goal is to develop CB-011 as a readily available off-the-shelf treatment option for patients with relapsed or refractory multiple myeloma to overcome the need for apheresis or bridging therapy, variable quality and long manufacturing timelines, manufacturing failures, or the inability to bear the burden of treatments that require frequent dosing over several months.”

CB-011 is an allogeneic BCMA-targeted CAR-T cell therapy engineered using Cas12a chRDNA technology. It uses an immune cloaking strategy with a beta-2 microglobulin (B2M) protein knockout and insertion of a B2M–human-leukocyte-antigen-E–peptide transgene fusion protein to blunt immune-mediated rejection and to improve antitumor activity.

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CB-011 is being evaluated in the phase 1 CaMMouflage trial (NCT05722418), which dosed its first participant with relapsed/refractory multiple myeloma in March 2023.² The patient received a dose of 50x10⁶ cells of CB-011 cells after cyclophosphamide and fludarabine lymphodepletion. Caribou Biosciences anticipatesadditional enrollment and dosing of patients at this dose level before moving on to the trial’s higher dose levels. The FDA cleared the investigational new drug application for CB-011 in November of last year.³

CaMMouflage is planned to be a 2-part trial, starting with a 3+3 ascending dose escalation phaseto be proceeded with an expansion phase in which up to 30 participants will be enrolled to receive CB-011 at the recommended phase 2 dose. The dose escalation phase is primarily assessing dose-limiting toxicities and the expansion phase is primarily assessing overall response rate.

“Approved therapies have demonstrated efficacy in patients with relapsed or refractory multiple myeloma, but challenges remain with patient access, tolerability, and treatment burden,” Sundar Jagannath, MD, professor of medicine and Mount Sinai endowed chair for multiple myeloma at Mount Sinai School of Medicine, and director of the Multiple Myeloma Center of Excellence at Tisch Cancer Institute, Mount Sinai Hospital, New York, said in an earlier statement.² “There is a significant unmet need for an off-the-shelf CAR-T cell therapy as a readily available treatment option that does not require multiple rounds of treatment.”

REFERENCES

1. Caribou Biosciences announces FDA granted fast track designation to CB-011, an allogeneic CAR-T cell therapy for relapsed or refractory multiple myeloma. News release. Caribou Biosciences. April 4, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-granted-fast-track-designation
2. Caribou Biosciences announces dosing of first patient in the CaMMouflage phase 1 trial of CB-011, an allogeneic anti-BCMA CAR-T cell therapy for the treatment of relapsed or refractory multiple myeloma. News release. Caribou Biosciences, Inc. March 29, 2023. Accessed March 30, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-dosing-first-patient-cammouflage
3. Caribou Biosciences announces FDA clearance of IND application for CB-011, an allogeneic anti-BCMA CAR-T cell therapy for the treatment of relapsed or refractory multiple myeloma. News release. Caribou Biosciences. November 21, 2022. https://finance.yahoo.com/news/caribou-biosciences-announces-fda-clearance-140000360.html