Caribou’s CB-011 may be effective, safe for hard-to-treat myeloma
Lasting responses seen with 'off-the-shelf' cell therapy in ongoing trial
One-time use of CB-011, Caribou Biosciences’ off-the-shelf CAR T-cell therapy candidate, showed a manageable safety profile and resulted in lasting responses in adults with treatment-resistant or relapsed multiple myeloma.
That’s according to the first data from the ongoing Phase 1 CaMMouflage clinical trial (NCT05722418), which is underway at 16 sites across the U.S. The data were presented this week in a company webcast announced by Caribou in a press release that details how to view the presentation. It will be available through early next month.
The trial, open to patients 18 and older, is still recruiting participants who have received at least three prior lines of multiple myeloma therapy.
In the webcast, Adriana Rossi, MD, a CaMMouflage investigator, noted that the researchers “see deep and durable responses … in this very heavily pretreated [patient] population.”
CB-011 has “the potential to expand access and bring … meaningful benefit to patients who urgently need a readily available, single-dose option,” said Rossi, also the director of CAR-T and the stem cell transplant clinical program at Mount Sinai’s center of excellence for multiple myeloma.
CB-011, made from donor cells, is a ready to use treatment
Myeloma occurs when plasma cells, a type of immune cell made in the bone marrow, become abnormal and grow out of control.
CB-011 is an allogeneic CAR T-cell therapy that involves collecting immune T-cells from healthy donors and genetically modifying them to produce a chimeric antigen receptor, or CAR, that recognizes and binds to BCMA, a protein found on the surface of myeloma cells.
Before receiving CB-011, patients are given a chemotherapy regimen for lymphodepletion, which means killing existing immune cells and making room for the engineered ones.
Unlike traditional autologous CAR T-cell therapies, which involve collecting a patient’s own T-cells, CB-011 is allogeneic, providing a ready to use or so-called off-the-shelf alternative. The experimental therapy was granted fast track designation in the U.S. in 2023. That status is intended to speed the clinical development of treatments meant to fill an unmet need in medical care.
To date, a total of 48 adults with hard-to-treat multiple myeloma have been dosed in the dose-escalating portion of the CaMMouflage study. All had received a median of four previous lines of therapy, including a proteasome inhibitor, an immunomodulator, and an anti-CD38 antibody.
Slightly more than two-thirds of the participants thus far are men, and the patients’ median age is 68.5.
Overall response rate of over 90% seen so far in trial
A group of 35 participants received a selected lymphodepletion regimen followed by CB-011 at doses ranging between 150 and 800 million cells. The results for those patients who had not previously received other anti-BCMA therapies showed that the 450 million cells dose was associated with the best responses across all outcomes measures.
All but one of the 13 patients who received this dose had not been given prior anti-BCMA therapies and were followed for as long as about 15 months, or slightly longer than one year, after the single treatment dose.
Among these 12 participants, a single dose of CB-011 resulted in an overall response rate of 92%, with 75% of people showing a complete response, or no signs of cancer, and 83% showing at least a very good partial response, or cancer reduction.
Most patients with evaluable data (91%) were negative for minimal residual disease or MRD, defined as a very small number of cancer cells that remain in the body after treatment. Having such cells still in the body can increase the risk of relapse.
In addition, seven of the patients (nearly 60%) were still experiencing at least a very good partial response at six months or more after treatment.
The 450 million cells dose was therefore selected for the trial’s dose-expansion portion, where more patients will be treated with the therapy at that dose.
[CB-011 is] delivering on the promise of CAR T-cell therapies.
Overall, the therapy was safe and well-tolerated, with manageable adverse events. The most commonly reported adverse events in the group of 35 patients were infections (49%) and cytokine release syndrome (31%), which is an inflammatory reaction.
The results also showed that a greater CB-011 expansion within the patient’s body was associated with better responses, and that patients experienced fast recovery of immune cells, “reinstating their natural immunity and contributing to this impressive favorable safety profile,” according to Rossi.
“Balancing this [CAR T-cell] activity with a rapid recovery [of natural immune activity] is really a unique profile that we see with Caribou’s allogeneic CAR-T programs,” Rossi said in the webcast.
The company is also developing CB-010, which is similar to CB-011, but is designed to target CD19, a protein found on the cancer cells implicated in large B-cell lymphoma, another type of blood cancer.
According to Rachel Haurwitz, PhD, president and CEO of Caribou, who spoke during the webcast, both treatments “are delivering on the promise of CAR T-cell therapies.”
