Caribou Biosciences Provides Updates on Allogeneic CAR-T Clinical Trials

Caribou Biosciences has announced that the first patient has been dosed in its phase 1 CaMMouflage clinical trial (NCT05722418) evaluating CB-011 for the treatment of relapsed/refractory (r/r) multiple myeloma (MM) and that it has initiated the dose expansion portion of its phase ANTLER clinical trial (NCT04637763) evaluating CB-010 for the treatment of r/r B-cell non-Hodgkin lymphoma (B-NHL).^1,2

The first patient treated in the CaMMouflage trial received a dose of 50x10⁶ cells of CB-011, which is an allogeneic anti-BCMA chimeric-antigen receptor T-cell (CAR-T) therapy. Caribou Biosciences anticipates additional enrollment and dosing of patients at this dose level before moving on to the trial’s higher dose levels. CB-011 incorporates an “immune cloaking approach” involving elimination of the endogenous beta-2 microglobulin protein and the insertion of a B2M–human-leukocyte-antigen-E–peptide transgene. The approach is intended to prevent rejection of the CAR-T by patients’ immune systems. The news of the first patient’s dosing comes several months after the company announced the FDA’s clearance of its investigational new drug application for CB-011 in November of last year.³

“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 a statement regarding the news.¹ “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.”

Meanwhile, the dose-expansion portion of the ANTLER trial will evaluate CB-010—an anti-CD19 CAR-T—at doses of 80x10⁶ cells and 120x10⁶ cells.² Approximately 15 patients with second-line r/r B-NHL will be treated at each of the 2 dose levels. Caribou Biosciences noted that additional patients might be enrolled after the recommended phase 2 dose is determined and that it anticipates a new announcement of safety and efficacy data from the ANTLER trial in the second half of this year.

“We have heard time and again from the lymphoma community about the challenges of autologous CAR-Ts, such as apheresis, bridging therapy, long wait times for manufacturing, or manufacturing failures,” Syed Rizvi, MD, the chief medical officer of Caribou Biosciences, said in a statement regarding the news.² “CB-010 addresses these challenges as the therapy is manufactured from healthy donor cells and is available off-the-shelf for eligible clinical trial patients. Evaluating CB-010 in the second-line setting places Caribou at the forefront of the off-the-shelf cell therapy field by potentially addressing the unmet needs of patients with a readily available therapeutic option at an earlier stage of their disease.”

Caribou Biosciences reported that CB-010 was generally well-tolerated in the dose-escalation portion of ANTLER, with no dose-limiting toxicities occurring in the 3 participants who received the 120x10⁶ cell dose. In terms of efficacy, the company noted that 6 of 6 patients treated at a dose of 40x10⁶ cells in the trial’s first cohort achieved a complete response (CR). Three of these patients maintained their CR at 6 months and 2 maintained their CR at 12 months. In October of last year, the company presented a case report on a patient with follicular lymphoma who maintained a CR at 15 months after being treated with CB-010 at the Lymphoma, Leukemia, & Myeloma Congress, held in New York City, New York on October 18-22, 2022.⁴ In November 2022, it was announced that the FDA had granted CB-010 fast-track designation for the treatment of r/r B-NHL and regenerative medicine advanced therapy designation for the treatment of r/r large B cell lymphoma.⁵

REFERENCES

1. 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

2. Caribou Biosciences initiates dose expansion portion of CB-010 ANTLER phase 1 trial in second-line LBCL patients. News release. Caribou Biosciences, Inc. March 29, 2023. Accessed March 30, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-initiates-dose-expansion-portion-cb-010

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

4. Caribou Biosciences presents case report on long-term follow up of first patient dosed in phase 1 ANTLER trial at the Lymphoma, Leukemia, & Myeloma Congress 2022. News release. Caribou Biosciences. October 18, 2022. Accessed March 31, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-presents-case-report-long-term-follow-first

5. 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. Accessed March 31, 2023. 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