Caribou's Allogeneic CAR-T CB-012 Cleared for US Trial in R/R AML

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In light of the IND clearance, the company is planning to carry out plans for a phase 1 clinical trial (AMpLify) for adult patients with r/r AML.

Caribou Biosciences’ CB-012, an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy directed at C-type lectin-like molecule-1 (CLL-1) and intended to treat relapsed/refractory (r/r) acute myeloid leukemia (AML), has received clearance of its investigational new drug (IND) application from the FDA.1

“CB-012 was engineered with 5 genome edits, and is the first allogeneic CAR-T cell therapy, to our knowledge, with both checkpoint disruption through a PD-1 knockout, and immune cloaking through a B2M knockout and B2M–HLA-E fusion transgene insertion,” Steve Kanner, PhD, Caribou’s chief scientific officer, said in a statement.1 “Both armoring strategies are designed to improve the antitumor activity of CB-012 that we believe are crucial for targeting this difficult to treat indication.”

In light of the IND clearance, the company is planning to carry out plans for a phase 1 clinical trial (AMpLify) for adult patients with AML that is nonproliferative and r/r following 3 or fewer standard lines of therapy. The first portion of the multicenter trial will follow a 3+3 dose escalation format; Caribou anticipates beginning enrollment for patients to be treated at the study’s lowest dose level (25x106 CAR-T cells) by the middle of next year. The second, dose-expansion portion of the trial will seek to determine antitumor activity via overall response rate (ORR).

“There is an urgent need to develop new treatments for patients with relapsed or refractory AML, for which the treatment options are predominantly limited to salvage chemotherapy regimens,” Naval Daver, MD, an associate professor and director of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, added to the statement.1 “An allogeneic CAR-T cell therapy that could safely and effectively target AML blasts while preserving healthy hematopoietic stem cells could provide a much-needed off-the-shelf option for these patients.”

CB-012 is one of 4 cell therapies that Caribou is currently developing for cancer indications.2 In addition to CB-012 and a CAR natural killer cell therapy aimed at solid tumors, CB-020, which remains in the discovery phase of preclinical development, the company has 2 other allogeneic CAR-T therapies in clinical development for the treatment of hematological malignancies: CB-010 and CB-011.

Earlier this year, in June, Caribou reported that CB-010, its CD19-directed CAR-T produced durable responses among patients with r/r B-cell non-Hodgkin lymphoma (B-NHL) who were treated in the phase 1 ANTLER clinical trial (NCT04637763).3 Among 16 patients who were treated with CB-010 as of the June 20, 2023, efficacy data cutoff date, the ORR was 94% (n = 15) and the complete response (CR) rate was 69% (n = 11). Furthermore, 7 patients (44%) had CRs at 6 months posttreatment or later and 1 patient’s CR has been maintained for 24 months and remains ongoing.

Prior to that, in April 2023, the company announced that CB-011, its BCMA-targeted CAR-T intended to treat r/r multiple myeloma, had been granted fast track designation by the FDA.4 CB-011 is being evaluated in the phase 1 CaMMouflage trial (NCT05722418), which dosed its first participant with r/r multiple myeloma in March 2023.5

“Approved therapies have demonstrated efficacy in patients with r/r multiple myeloma, but challenges remain with patient access, tolerability, and treatment burden,” Sundar Jagannath, MD, a 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 March 2023 statement.5 “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 clearance of IND application for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy for the treatment of relapsed or refractory acute myeloid leukemia. News release. Caribou Biosciences, Inc. October 18, 2023. Accessed October 26, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-clearance-ind-application-cb-0
2. Caribou Biosciences. Pipeline. Website. Accessed October 26, 2023. https://www.cariboubio.com/pipeline/
3. Caribou Biosciences reports positive clinical data from dose escalation of CB-010 ANTLER phase 1 trial in r/r B-NHL. News release. Caribou Biosciences, Inc. July 13, 2023. Accessed October 26, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-reports-positive-clinical-data-dose
4. 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 October 26, 2023.https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-granted-fast-track-designation
5. Caribou Biosciences announces dosing of first patient in theCaMMouflage 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 October 26, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-dosing-first-patient-cammouflage
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