Clinical Summary: 

• Design/Population: The phase 1 CaMMouflage trial evaluated CB-011, an allogeneic anti-BCMA CAR T-cell therapy manufactured from healthy donor T cells and engineered with immune-cloaking technology, in 48 patients with relapsed or refractory multiple myeloma who had received at least 3 prior lines of therapy. 
• Key Outcomes: Among BCMA-naïve patients treated at the recommended dose, CB-011 achieved a 92% overall response rate, with 75% achieving a complete response or better and 91% achieving MRD negativity. Responses were durable, and the safety profile was manageable, with low rates of severe CRS and no grade ≥3 ICANS or graft-versus-host disease.
• Clinical Relevance: These findings support the potential of off-the-shelf allogeneic CAR T-cell therapy to deliver deep and durable responses while addressing manufacturing delays and access limitations associated with autologous CAR T-cell products. 

Binod Dhakal, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, discusses updated results from the phase 1 CaMMouflage study evaluating CB-011 in patients with relapsed or refractory multiple myeloma. CB-011 incorporates four CRISPR-Cas12a genome edits designed to enhance persistence and reduce immune-mediated rejection, representing a novel approach to allogeneic CAR T-cell therapy.

The study demonstrated high response rates, deep MRD-negative remissions, and encouraging durability in a heavily pretreated population characterized by high-risk cytogenetics and extramedullary disease. Importantly, the therapy maintained a favorable safety profile with low rates of severe CRS and neurotoxicity, supporting continued development of CB-011 as a scalable, off-the-shelf cellular therapy for patients with relapsed/refractory multiple myeloma.

Dr Dhakal presented these results at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript:

Hello, my name is Binod Dhakal. I’m a Professor of Medicine at the Medical College of Wisconsin.

At EHA 2026 in Stockholm, Sweden, I presented long-term follow-up results from the ongoing CaMMouflage phase 1 clinical trial, which is evaluating CB-011, an allogeneic anti-BCMA CAR T-cell therapy with immune cloaking, in patients with relapsed or refractory multiple myeloma.

CB-011 is manufactured from healthy donor T cells and incorporates 4 genome edits using CRISPR-Cas12a technology. These include insertion of a BCMA-specific CAR, knockout of the TRAC gene to reduce the risk of graft-versus-host disease, knockout of beta-2 microglobulin to reduce T-cell–mediated rejection, and insertion of a beta-2 microglobulin–HLA-E fusion to blunt NK-cell–mediated rejection.

As an allogeneic, off-the-shelf CAR T-cell therapy, CB-011 has the potential to address several limitations associated with currently available therapies, including both bispecific antibodies and autologous CAR T-cell therapies. Unlike bispecific antibodies, which often require continuous administration, a single dose of CB-011 can produce deep responses. And unlike autologous CAR T-cell therapies, which require individualized manufacturing and weeks of production time, CB-011 can be administered rapidly and manufactured at scale.

The CaMMouflage study is a phase 1 trial utilizing a standard 3+3 dose-escalation design followed by dose expansion. Eligible patients had relapsed or refractory multiple myeloma with at least 3 prior lines of therapy, including prior exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Patients received one of two lymphodepletion regimens consisting of fludarabine 30 mg/m² for 3 days together with either cyclophosphamide 300 mg/m² or cyclophosphamide 500 mg/m². This was followed by a single infusion of CB-011 at doses ranging from 50 million to 800 million CAR T cells.

As of September 2025, a total of 48 patients had received CB-011. The median age was 68.5 years, and patients had received a median of four prior lines of therapy. Seventeen percent had prior BCMA-targeted therapy exposure, 56% had high-risk cytogenetics, and 35% had extramedullary disease.

During dose escalation, 1 patient treated in the 300 mg/m² cyclophosphamide cohort experienced CAR T-cell expansion and achieved an MRD-negative stringent complete response that remains ongoing more than 21 months later. Based on the overall data, the 500 mg/m² cyclophosphamide regimen was selected to optimize CAR T-cell expansion.  The recommended dose for expansion is 450 million CAR T cells following lymphodepletion with cyclophosphamide 500 mg/m² and fludarabine.

Looking specifically at the BCMA-naive patients treated at the recommended dose for expansion, the overall response rate was 92%, and 75% of patients achieved a complete response or better. Among MRD-evaluable patients, 10 of 11, or 91%, achieved MRD negativity at the 10^-5 threshold. At a median follow-up of 8.3 months, 58% of patients remained in a VGPR or better for at least 6 months.

In terms of safety, CB-011 demonstrated a manageable safety profile. Among patients treated with the 500 mg/m² cyclophosphamide regimen, infections occurred in 49% of patients, with grade 3 or higher infections occurring in 14%. CRS occurred in 31% of patients, with only 3% experiencing grade 3 or higher CRS. ICANS occurred in 9% of patients, and there were no grade 3 or higher ICANS events. Immune effector cell–associated HLH-like syndrome occurred in 9% of patients, including 1 grade 3 or higher event. Prolonged grade 3 or higher cytopenias occurred in 33% of patients.

Importantly, there were no cases of graft-versus-host disease, immune effector cell–associated enterocolitis, parkinsonism, or cranial nerve palsies at any dose level. There was one grade 4 Guillain-Barré syndrome event that continues to improve. Three deaths occurred—one related to pneumonia, one related to RSV infection, and one related to ICAHT. These observations led to implementation of additional prophylactic and early-intervention measures within the study.

We also evaluated the biological behavior of the product. CB-011 expansion directly correlated with clinical response and was greater in patients who received the 500 mg/m² cyclophosphamide lymphodepletion regimen compared with the 300 mg/m² regimen. At peak expansion, CB-011 demonstrated a central memory CD8-positive T-cell phenotype, which may contribute to durability.

Importantly, endogenous T cells and NK cells recovered rapidly after treatment, and endogenous B cells recovered within 6 months regardless of response status. This rapid immune reconstitution may contribute to the favorable safety profile observed with CB-011.

In conclusion, in a high-risk and heavily pretreated relapsed/refractory multiple myeloma population, CB-011 produced deep and durable responses with a manageable safety profile. Based on these results, the recommended dose for expansion is 450 million CAR T cells following lymphodepletion with cyclophosphamide 500 mg/m² and fludarabine. The dose-expansion phase of the CaMMouflage study is currently enrolling both BCMA-naive and BCMA-exposed patients, and updated data will be presented in the future. 

Source: 

Dhakal B, Rossi A, Clark W, et al. CB-011, an allogeneic anti-BCMA CAR-T cell therapy with immune cloaking, for patients with relapsed/refractory multiple myeloma (CaMMouflage phase 1 trial). Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-4901.