Phase 1 Trial to Test ‘Off-the-shelf’ CAR T-cell Therapy CB-011 in 2023
CB-011 will be tested in myeloma patients with 3 or more prior lines of therapy
Caribou Biosciences will soon start testing its new CAR T-cell therapy candidate, CB-011, in people with relapsed or refractory multiple myeloma.
A Phase 1 trial will begin enrolling eligible adults in early 2023 at multiple centers, according to the company.
The announcement follows clearance of the company’s investigational new drug (IND) application by the U.S. Food and Drug Administration, which grants a company permission to conduct human clinical trials. Caribou had previously received clearance for CB-010, an experimental CAR T-cell therapy for relapsed or refractory B-cell non-Hodgkin’s lymphoma.
“Clearance of our second IND application represents another key milestone for our pipeline of promising allogeneic [donor] cell therapies designed to have enhanced persistence of antitumor activity,” Rachel Haurwitz, PhD, president and CEO of Caribou, said in a press release.
What is CAR T-cell therapy?
CAR T-cell therapy typically involves using a patient’s own T-cells and genetically altering them to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein. When the T-cells are obtained from the patient, this is called autologous therapy. If they are taken from a compatible donor, this type of treatment is known as allogeneic therapy.
A disadvantage of allogeneic therapy is that a patient’s immune system, namely their T-cells and natural killer (NK) cells, can reject the CAR T-cell therapy. Additionally, a donor’s T-cells can attack and damage a patient’s healthy cells, a condition known as graft-versus-host disease, which can be life-threatening.
To prevent these complications, Caribou uses its genome-editing technology, called Cas12a CRISPR hybrid RNA-DNA (chRDNA). While CB-011 is an allogeneic CAR T-cell therapy specifically engineered to target a protein called B-cell maturation antigen present in cancer cells, the therapy is also modified to reduce the risk of graft-versus-host disease.
CAR-T cell therapies have shown great promise for treating patients with relapsed or refractory multiple myeloma
Another alteration involves knocking out the beta-2-microglobulin gene of the CAR T-cells to prevent recognition and rejection by patients’ own T- and NK cells.
“CB-011 is designed with an immune cloaking strategy to reduce rejection of the cell therapy by a patient’s T and NK cells and we use Caribou’s highly precise and specific Cas12a chRDNA genome-editing technology to manufacture this product candidate,” Haurwitz said. “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, and we look forward to initiating patient enrollment in the CaMMouflage trial in early 2023.”
The open-label CaMMouflage clinical trial will evaluate CB-011 in patients with relapsed or refractory multiple myeloma who have had three or more prior lines of therapy. Prior treatment with other CAR T-cell therapies within the last three months is an exclusion criteria.
How will the CaMMouflage trial be conducted?
CaMMouflage will have two parts. In the first part, the trial will determine the maximum dose tolerated by patients. Patients are placed in groups of three, and each subsequent group is given a higher dose of CB-011. The first dose will be a single administration of 50×106 CAR T-cells.
Once an optimal dose has been defined in the first part of the trial, additional patients will be recruited to continue investigating that dose’s safety and potential efficacy.
“CAR-T cell therapies have shown great promise for treating patients with relapsed or refractory multiple myeloma,” said Sundar Jagannath, MD, director of the Multiple Myeloma Center of Excellence at Tisch Cancer Institute, Mount Sinai Hospital, in New York.
“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,” Jagannath added.