Trial data for 2 Caribou CAR T-cell therapies due this year
CB-010, CB-011 clinical data expected in 2nd half, company says
Caribou Biosciences is reprioritizing its pipeline to focus on two of its CAR T-cell therapies for blood cancer, including one, CB-011, that’s being developed for multiple myeloma.
The other is CB-010, which Caribou is developing to treat large B-cell lymphoma (LBCL). The company said it expects clinical data from Phase 1 studies testing these two therapies to be available in the second half of this year.
The ongoing Phase 1 CaMMouflage trial (NCT05722418), which is evaluating CB-011 in adults with multiple myeloma that has come back (relapsed) after treatment or is not responding to treatment (refractory), is recruiting participants at sites in the U.S. Those eligible will have received at least three prior lines of treatment, including a proteasome inhibitor, an immunomodulator, and an anti-CD38 antibody.
“Caribou’s two lead Phase 1 clinical programs … continue to demonstrate encouraging efficacy and have the potential to serve this critical unmet need for individuals living with hematologic malignancies [blood cancers],” Rachel Haurwitz, PhD, the company’s president and CEO, said in a company press release. “We recognize the challenges in the current market environment and believe the best approach is to present the most robust datasets for both programs.”
To secure the necessary resources for these priority programs, Caribou is reducing its workforce by about a third and discontinuing other preclinical and clinical programs, including one testing CB-010 for people with lupus and another testing CB-012 in people with acute myeloid leukemia.
Working toward ‘new era’ of allogenic cell therapies
“To ensure Caribou is strongly positioned to … deliver these potentially value-generating datasets, we have made the difficult decision to strategically prioritize our resources on CB-010 and CB-011 for oncology indications,” Haurwitz said.
CAR T-cell therapy leverages the natural cancer-killing abilities of immune T-cells. It involves genetically modifying T-cells to contain a chimeric antigen receptor, or CAR, that recognizes and binds to a protein on the surface of the cancer cells being targeted. This enhances T-cells’ ability to specifically find their way to the problematic cells and attack them.
Usually, the approach involves collecting a patient’s own T-cells and modifying them in the lab (an autologous therapy). Caribou’s CAR T-cell therapies are made ahead of time using cells from a healthy donor (an allogeneic therapy), making them an off-the-shelf, or ready-to-use, alternative.
“Broad patient access to life-changing CAR-T cell therapies is only achievable if healthcare systems have an off-the-shelf option,” Haurwitz said, noting that company is working toward “ushering in a new era of allogeneic CAR-T cell therapies that offer the potential for broad access and rapid availability to both patients and healthcare systems.”
Myeloma is caused when plasma cells, a type of immune cell made in the bone marrow, become abnormal and grow out of control.
With CB-011, T-cells are engineered with a CAR that recognizes BCMA, a protein found at high levels on these myeloma cells. Other modifications are made to prevent the recipient’s immune system from rejecting the donor cells and enhance the therapy’s anti-tumor activity. Before receiving CB-011, patients are given a lymphodepletion regimen consisting of chemotherapy to kill off existing immune cells and make room for the newly engineered ones.
CB-011 has received fast track designation in the U.S., a status intended to speed a treatment’s clinical development.
In the first part of the CaMMouflage trial, participants are receiving various doses of CB-011 and either of two lymphodepletion regimens in order to identify the optimal dosing strategy. All tested doses have so far shown no signs of toxicity.
Encouraging efficacy has also been observed in patients who received CB-011 at multiple dose levels and were given the stronger lymphodepletion regimen, according to Caribou. Participants who will receive this stronger chemotherapy are being enrolled.
The company plans to share initial safety and efficacy data later this year covering at least three months of follow-up at least 25 participants who received the higher-intensity lymphodepletion. The data will be used to determine the optimal dose for the study’s second part.
In that part, all participants will receive the selected optimized dose, with the goal of assessing the proportion of participants who achieve partial or complete tumor shrinkage after a year.
CB-010 works on a similar premise as CB-011, but it’s designed to target CD19, a protein found on the cancer cells implicated in LBCL. The ongoing Phase 1 ANTLER study (NCT05722418) , also recruiting in the U.S., is testing CB-010 in people with LBCL, with new data due this year.
Data thus far have also shown promising efficacy signals, and Caribou has been discussing plans for a pivotal clinical trial with U.S. regulators.
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