FDA Grants Fast Track Designation to CB-011 for R/R Multiple Myeloma

The FDA has granted a fast track designation to CB-011, a CRISPR-edited allogeneic chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with relapsed/refractory (R/R) multiple myeloma, according to Caribou Biosciences.¹

CB-011 is a genome-edited CAR T-cell product developed by Caribou Biosciences which works to target the B-cell maturation antigen (BCMA). CB-011 is the first allogeneic anti-BCMA CAR T-cell therapy made to improve duration of antitumor response through an immune cloaking approach that removes the B2M protein and inserts a B2M–HLA-E fusion protein, according to the company.²

Previously in November 2022, the FDA cleared an investigational new drug application for CB-011 in this patient population.2 This led to the initiation of a multicenter, open-label study titled CaMMouflage (NCT05722418).³

“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 [timelier,] as we recently dosed our first patient in the phase 1 CaMMouflage trial,” said Syed Rizvi, MD, chief medical officer at Caribou Biosciences, in a press release.¹

The phase 1 CaMMouflage trial aims to enroll approximately 50 patients with R/R multiple myeloma. To be included in the study, patients must have previously received 3 or more prior lines of therapy, have an ECOG performance status of 0 or 1, and have adequate hematologic, renal, hepatic, pulmonary, and cardiac function.³

Part A of the trial will be the escalation stage where a standard 3+3 dose-escalation design will be utilized. Investigators will assess ascending doses of CB-011 in combination with cyclophosphamide and fludarabine to determine the recommended phase 2 dose (RP2D) of the regimen. Then, part B will be the expansion stage where responses to the RP2D, or the maximum tolerated dose as measured by International Myeloma Working Group criteria, will be assessed.

The primary end point of part A of the study is to assess the dose limiting toxicities during the 28 days following the first administration of CB-011. In the second part, part B, the primary end point will evaluate the overall response rate among patients.

Patients are currently being recruited for the ongoing CaMMouflage study and are being treated with a single administration of CB-011 at a dose of 50 x 10⁶ CAR-T cells.

In addition to CB-011, the second allogeneic CAR T-cell product under investigation for the treatment of patients with hematologic malignancies, investigators are assessing CB-010. CB-010 is a CAR T-cell therapy that has a PD-1 knockout and is currently being evaluated in the phase 1 ANTLER trial (NCT04637763) of patients with relapsed or refractory B cell non-Hodgkin lymphoma.

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. Accessed April 10, 2023. https://investor.cariboubio.com/

2. 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. Accessed April 10, 2023. https://investor.cariboubio.com/news-releases/

3. CRISPR-edited allogeneic anti-BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma (CaMMouflage). Updated March 2, 10, 2023. Accessed April 6, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05722418