FDA Awards Fast Track Designation to CB-012 in Relapsed/Refractory AML

The FDA has granted fast track designation to the allogeneic anti–CLL-1 CAR T-cell therapy CB-012 for patients with relapsed/refractory acute myeloid leukemia (AML).¹

CB-012 is under investigation in this patient population in the ongoing phase 1 AMpLify trial (NCT06128044).

“We are pleased to receive fast track [designation] from the FDA. This is a testament to the significant unmet need and the potential of…CB-012 as [a] readily available, off-the-shelf CAR-T-cell [therapy],” Tina Albertson, MD, PhD, chief medical officer of Caribou Biosciences, stated in a news release. “Most patients with AML are refractory or relapse quickly after currently available therapeutic options, and allogeneic hematopoietic stem cell transplant is the only potentially curative option after salvage chemotherapy regimens. As we advance CB-012 and enroll patients at dose level 2, we are focused on our goal to deliver an effective, off-the-shelf treatment option for patients living with this disease.”

CB-012 is engineered with 5 genome edits that are enabled by the next-generation CRISPR technology platform, which uses chRDNA and Cas12a genome editing to improve genome edit specificity. CRISPR hybrid RNA-DNA guides—called chRDNAs—direct more precise genome editing compared with all-RNA guides and can be used to carry out multiple edits with high efficiency. CB-012 uniquely employs checkpoint disruption through PD-1 knockout, as well as immune cloaking through B2M knockout and B2M–HLA-E fusion protein insertion. These armoring strategies are designed to bolster antitumor activity.

The AMpLify trial is enrolling patients at least 18 years of age with relapsed/refractory AML with non-proliferative disease who have received a maximum of 3 prior lines of therapy.² Induction, consolidation with or without allogeneic stem cell transplant, and maintenance therapy phases are considered 1 line of therapy. Eligible patients must have no available therapy associated with a reasonable survival benefit; an ECOG performance status of 0 or 1; and adequate hepatic, renal, cardiac, and pulmonary function. Patients must also be fit for allogeneic stem cell transplant.

Patients will be excluded from the trial if they have acute promyelocytic leukemia; have extramedullary disease that is metabolically inactive by 18-FDG PET-CT; received prior treatment with CAR T-cell therapy; received allogeneic stem cell transplant within 100 days before lymphodepletion; have active graft-versus-host-disease requiring therapy; have a known active or prior history of central nervous system involvement; were vaccinated with a live, attenuated vaccine within 4 weeks prior to lymphodepletion; have an active hepatitis B or C infection; have a primary autoimmune or immunodeficiency disease; have a known life-threatening allergies, intolerance, or hypersensitivity to CB-012 or its excipients; or are seropositive for or have a history of HIV.

Part A of the trial is a dose-escalation phase evaluating increasing doses of CB-012 in a 3+3 design, during which the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) will be determined. Part B of the trial is a dose-expansion phase, during which patients will receive CB-012 at the MTD and/or RDE determined in part A to identify the recommended phase 2 dose. All patients in parts A and B will receive lymphodepletion with cyclophosphamide and fludarabine prior to CB-012 administration.

The primary end point of part A is the number of patients with dose-limiting toxicities during the 28 days following the first administration of CB-012. The primary end point of part B is overall response rate evaluated by European LeukemiaNet criteria.

References

1. Caribou Biosciences announces the FDA has granted fast track designations to CB-010 in refractory SLE and to CB-012 in relapsed or refractory AML. News release. Caribou Biosciences, Inc. September 3, 2024. Accessed September 3, 2024. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-has-granted-fast-track
2. CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy in patients with relapsed/refractory acute myeloid leukemia (AMpLify). ClinicalTrials.gov. Updated April 26, 2024. Accessed September 3, 2024. https://clinicaltrials.gov/study/NCT06128044