EHA 2026 | CAMMOUFLAGE trial: allogeneic anti-BCMA CAR-T shows durable responses in myeloma

CB-011 is the first differentiated anti-BCMA allogeneic CAR-T in multiple myeloma. It is designed with what you call an immune cloaking strategy, where there are two edits, important edits. One is beta-2 microglobulin is knocked out to limit the T cell-mediated rejection. And beta-2 microglobulin HLA protein is inserted to blunt the NK cell activity. So these two edits enhance the potency as well as the functional persistence. CAMMOUFLAGE Phase I clinical trial is a three plus three dose escalation followed by dose expansion trial evaluating the safety and efficacy of CB-011 in patients with relapsed/refractory multiple myeloma. The patients included in this study had at least three prior lines of therapy and had to have exposure to PI, IMiD, and anti-CD38 antibody. This study also allowed prior BCMA-targeted therapy patients as long as the washout was about 90 days. So at this meeting, I will be presenting the long-term follow-up results of the CAMMOUFLAGE Phase I trial, where about 48 patients were included in the study. The patients were very heavily treated with the median prior lines of therapy of four, up to 11 prior lines of therapy. And 56% of the patients had evidence of high-risk cytogenetics, including 33 patients with extra-medullary disease. In the study, we tested different dose levels ranging from 50 to 800 million CAR T-cells and also different lymphodepletion dosing regimens, including two. One is called standard lymphodepletion with 300 mg per square meter of cyclophosphamide and 30 mg of square meter of fludarabine for three days. The other one is selective lymphodepletion which is 500 milligrams of cyclophosphamide with 30 milligrams of square meter of fludarabine for three days. Now based on the phase one dose escalation safety and efficacy the recommended dose for expansion will be selective LD with 500 milligrams of cyclophosphamide with 30 milligrams of fludarabine plus 450 million CAR T-cells. Now, focusing on this patient only, the overall response rate in this patient in the BCMA-naive cohort was 92%. The complete response rate was 83% and 91% of MRD negativity. Up to 50% and more of these patients were still in CR and better at 15-month follow-up. So in terms of durability, it’s quite durable. In terms of safety, we observed very low rates of CRS and ICANS, including grade 3 and higher infections. There are no delayed neurotoxicities. That includes Parkinson’s syndrome, cranial palsy, graft-versus-host disease, immune-effector colitis. So at the recommended dose for expansion, CB-011 demonstrates very high response rate and durable responses, including activity in prior BCMA CAR-T-treated patients. The enrollment right now is going on expansion phase for both BCMA-naive and BCMA-exposed patients, and it will be interesting to see how these patients do that will inform the Phase II study design in the future. As you know, there are a lot of CAR-T products right now in multiple myeloma, including both autologous product, as well as some of the other off-the-shelf product like bispecific, trispecific. So I think CB-011 has a unique advantage that could overcome some of the challenges for both of these agents. For example, unlike bispecific and trispecific, which is given continuously, either weekly or every other week, CB-011 with a single dose as an off-the-shelf therapy can produce high response rates with low rates of infections and other toxicities. Similarly, unlike auto CAR-T, which takes weeks to months to deliver to the patient, this can be delivered immediately between eligibility and lymphodepletion. And also, unlike auto CAR-T, which is an individualized therapy with one dose per manufacturing batch, this can be manufactured at a scale of 50 to 100 doses per manufacturing batch.