FDA Grants Fast Track Designation to CAR T-Cell Therapy That Achieved 100% Complete Response in Lymphoma Patients

The FDA has issued a Regenerative Medicine Advanced Therapy (RMAT) designation to CB-010, which is indicated to treat relapsed or refractory large B cell lymphoma (LBCL). CB-010 also received Fast Track designation for relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), announced Caribou Biosciences, Inc, the biopharmaceutical company behind the new clinical-stage therapy.

“RMAT and Fast Track designations for CB-010 are important recognitions of the significant unmet patient need for an off-the-shelf cell therapy in the treatment of aggressive B-NHL,” said Rachel Haurwitz, PhD, president, chief executive officer, Caribou, in a recent press release.

In data presented at the European Hematology Association (EHA) 2022 Congress, 100% of participants in the ANTLER phase 1 trial had a durable complete response (CR) with CB-010. This was determined to be the best response following dose level 1 treatment with CB-010.

CB-010 is an allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cell therapy with PD-1 knockout capabilities. It is engineered to place a specific CD19 CAR into the TRAC gene, which will knock out PD-1 and boost antitumor activity, according to the study authors. By limiting premature CAR-T cell exhaustion, the new therapy is also designed to improve the persistence of this antitumor activity.

The ANTLER trial evaluated the drug’s safety at a dose level 1 of 40x106 CAR T cells. At follow-up of 6 months, 50% of participants maintained a durable CR. Overall, 1 patient even experienced a CR at 15 months post-treatment with dose level 1 (40x106 CAR T cells) of CB-010.

Haurwitz explained that half of all patients who were treated with dose level 1 of CB-010 “maintained a durable complete response at 6 months.”

“CB-010 has been designed with a PD-1 knockout strategy to improve the persistence of antitumor activity by limiting premature CAR-T cell exhaustion,” Haurwitz said in the press release.

CRISPR genome editing changes DNA in living cells. CB-010 is a Class 2 CRISPR system with 2 constituents: the nuclease protein, which splits DNA and RNA molecules to unveil the genome that needs editing; and the CRISPR hybrid RNA-DNA guides (chRDNAs). The nuclease protein may edit a wrong genomic sequence (off-target editing), but the hybrid guide can allow the protein to make precise genome editing, according to the study authors.

The FAST Track and RMAT designations could expedite the development and review of CB-010 for patients suffering from LBCL and HCL. The designations could improve the chances for Priority Review, Rolling Review, and Accelerated Approval in the near future, according to Caribou Biosciences.

“We are encouraged that CB-010 has demonstrated early potential as an off-the-shelf cell therapy that may meaningfully rival autologous cell therapies,” Haurwitz said in the press release.

Reference

Caribou Biosciences, Inc. Caribou Biosciences Announces the FDA Granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track Designations to CB-010, an Allogeneic Anti-CD19 CAR-T Cell Therapy. News Release. November 29, 2022. Accessed on November 30, 2022. https://www.cariboubio.com/