FDA Recognizes Allogeneic CAR T Therapy for Lymphomas

The FDA has granted fast track designation to Caribou Biosciences’ chimeric antigen receptor (CAR) T-cell therapy CB-010 for treating relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) and regenerative medicine advanced therapy designationfor treating R/R large B cell lymphoma (LBCL).¹

“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,” Rachel Haurwitz, PhD, president and chief executive officer, Caribou Biosciences, said in a statement.¹ “Through genome editing with our precision CRISPR chRDNA genome-editing technology, 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. In our ANTLER Phase 1 trial, 3 of 6 patients treated with CB-010 at dose level 1 maintained a durable complete response at 6 months. We are encouraged that CB-010 has demonstrated early potential as an off-the-shelf cell therapy that may meaningfully rival autologous cell therapies.”

CB-010 is being evaluated in the phase 1 ANTLER trial (NCT04637763) in patients with diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and primary mediastinal large B-cell lymphoma.² Data most recently presented from the ANTLER trial at the European Hematology Association (EHA) 2022 Congress in June showed that all 6 patients dosed with 40x10⁶ CB-010 cells in cohort 1 had complete responses (CRs) which continued up to 6 months in 2 of 5 patients that reached that follow-up. Altogether, 3 patients have a continuing response. The longest follow-up is 12 months in the first patient withB-NHL who has a continuing CR.

READ MORE: Allogeneic CAR T Yields 15-Month CR in Follicular Lymphoma

CB-010 had a manageable safety profile. All study participants experienced treatment-emergent adverse events (AEs) and 4 participants experienced treatment-related AEs of grade 3 or higher including neutropenia, thrombocytopenia, and white blood cell count decrease. Two patients also developed low grade cytokine release syndrome, 1 developed grade 3 immune effector cell-associated neurotoxicity syndrome, and 2 patients developed grade 2 and 3 infections. No graft-versus-host disease has been observed.

“We believe the 100% complete response achieved in the ANTLER CB-010 trial is unparalleled for a single, starting dose of cell therapy and represents an important step toward showing the potential of our chRDNA genome-editing platform and pipeline of allogeneic cell therapies,” Haurwitz said in a previous statement.² “As the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout, CB-010 is designed to have sustained antitumor activity by limiting premature CAR-T cell exhaustion in patients with r/r B-NHL. As we enroll patients in cohort 2 at dose level 2 of the ANTLER trial, we are grateful for the patients, caregivers, and investigators who have participated in this clinical trial. We continue to advance CB-010, as our goal is to develop an allogeneic cell therapy that may meaningfully rival autologous cell therapies and extend the potential reach of off-the-shelf treatments for patients.”

CB-010 is an allogeneic anti-CD19 CAR T-cell therapy, designed to improve the persistence of antitumor activity and limit CAR T-cell exhaustion.¹ The therapy is genome-edited by use of Caribou’s next-generation CRISPRplatform that uses Cas9 CRISPR hybrid RNA-DNA to insert a CD19-specific CAR into the TRAC gene and knock out PD-1.

REFERENCES 

1. 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. Caribou Biosciences. November 29, 2022. https://www.globenewswire.com/news-release/2022/11/29/2564105/0/en/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.html
2. Nastoupil LJ, O’Brien S, Holmes HE, et al. First-in-human trial of CB-010, a CRISPR-edited allogeneic anti-cd19 CAR T-cell therapy with a pd-1 knock out, in patients with relapsed or refractory b cell non-Hodgkin lymphoma (Antler study). Presented at: EHA 2022 Congress, June 9-12, Vienna, Austria and virtually. Abstract #3103