FDA Clears IND Application for Anti–CLL-1 CAR T-Cell Therapy for R/R AML

CB-012 is a genome-edited CAR T cell therapy that is produced using the next-generation genome-editing technology platform CRISPR Cas12a chRDNA, which is capable of generating notable genomic integrity and significant specificity.

The FDA has cleared an investigational new drug application for allogeneic anti–CLL-1 chimeric antigen receptor (CAR) T Cell therapy CB-012 as a treatment for patients with relapsed/refractory acute myeloid leukemia (AML), according to a press release from Caribou Biosciences.¹

Investigators report that CB-012 will be assessed as part of the phase 1 AMpLify study (NCT04853017) in the aforementioned patient population. Experts indicate that CLL-1 has potential as a therapeutic target in the AML space, as it is highly expressed in cancer cells and leukemic stem cells, although it is not seen on hematopoietic stem cells.

“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, associate professor and director of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said in the press release. “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 a genome-edited CAR T cell therapy that is produced using the next-generation genome-editing technology platform CRISPR Cas12a chRDNA, which is capable of generating notable genomic integrity and significant specificity. The agent is capable of checkpoint disruption and immune cloaking. CB-012 was designed to target CLL-1–positive AML while decreasing the risk of graft-vs-host disease and immune rejection of T cells and natural killer cells.²

“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, explained. “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.”

The open-label, multicenter phase 1 AMpLify study will evaluate CB-012 using a 3+3 design in the trial’s dose escalation portion. Investigators will assess the agent at several ascending doses to decide upon a maximum tolerated dose and/or recommended dose for the dose expansion portion of the study. Notably, the primary outcome of the dose expansion portion of the study is the overall response rate following 1 dose of CB-012.

The trial will include individuals who have not responded to or relapsed following standard treatment. Those who have proliferative disease or have undergone treatment with over 3 previous lines of therapy are ineligible for enrollment. Investigators intend to begin patient enrollment by mid-2024, wherein patients will receive a single infusion of CB-012 at 25x106 CAR T cells or dose level 1.

“We look forward to initiating patient enrollment in the AMpLify Phase 1 trial by the middle of 2024 to evaluate the safety and tolerability of CB-012 in patients suffering from AML,” Rachel Haurwitz, PhD, president and chief executive officer at Caribou Biosciences, concluded.

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. October 18, 2023. Accessed October 25, 2023. https://bit.ly/3tELm8Q
2. Caribou Biosciences. CAR-T cell therapy platform. 2023. Accessed October 25, 2023. https://bit.ly/45M0nmN