The phase 1 clinical trial plans to initiate enrollment in early 2023.
The FDA has cleared Caribou Biosciences’ investigational new drug application (IND) for CB-011, an allogeneic, BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy for treating relapsed/refractory multiple myeloma (r/r MM).1
“Clearance of our second IND application represents another key milestone for our pipeline of promising allogeneic cell therapies designed to have enhanced persistence of antitumor activity,” Rachel Haurwitz, PhD, president and chief executive officer, Caribou Biosciences, said in a statement.1 “CB-011 is designed with an immune cloaking strategy to reduce rejection of the cell therapy by a patient’s T and natural killer (NK) cells and we use Caribou’s highly precise and specific Cas12a chRDNA genome-editing technology to manufacture this product candidate. We are excited to develop CB-011 as an off-the-shelf cell therapy that may reach a broader number of patients with multiple myeloma than are currently being served.”
The therapy will be evaluated for safety and efficacy in the phase 1 CaMMouflage clinical trial. Caribou expects to start enrolling patients with r/r MM to be treated at the first dose level of 50x106 CAR T-cells in early 2023.
CB-011 is genome-edited with Caribou’s Cas12a CRISPR hybrid RNA-DNA (chRDNA) technology to achieve an immune cloaking strategy by removing the B2M protein and insert a B2M–HLA-E fusion protein for enhanced persistence of antitumor response. This editing takes 4 steps: the first 2 insert a humanized anti-BCMA CAR into the TRAC gene, which knocks out reception of the T cell to reduce the risk of graft versus host disease. The next 2 steps are insertion of the B2M–HLA-E peptide fusion gene into the B2M gene of the CAR T-cells to prevent rejection of patient T and NK cells, which also knocks out endogenous B2M expression and further reduces patient immune rejection.
“CAR-T cell therapies have shown great promise for treating patients with relapsed or refractory multiple myeloma,” Sundar Jagannath, MD, director, Multiple Myeloma Center of Excellence, Tisch Cancer Institute, Mount Sinai Hospital, New York, added to the statement.1 “Allogeneic, or ‘off-the-shelf,’ CAR-T cell therapies would provide a great option for patients with multiple myeloma, helping to overcome the need for bridging therapies as well as variable quality and manufacturing timelines of autologous CAR-T cells.”
CB-011 is Caribou’s second allogeneic CAR T-cell therapy to enter clinical trials, following CB-010, which is being evaluated in the phase 1 ANTLER trial (NCT04637763) in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). CB-010 is a CD19-targeted CAR T-cell therapy with a PD-1 knockout. Updated data from June 2022 showed that the therapy yielded a 100% complete response (CR) rate in 6 participants, and a case study presented in October 2022 showcased an ongoing, 15-month CR.2,3 Additional follow-up data from the first cohort will be presented by the end of 2022.