In the dose escalation portion of the CaMMouflage phase 1 clinical trial, safety and efficacy of CB-011 were evaluated in 48 fourth-line and later (4L+) patients at multiple dose levels and following two different lymphodepletion regimens. Thirty-five patients were treated with the selected lymphodepletion (LD) regimen of 500 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for three days. A single dose of CB-011 preceded by the selected LD regimen resulted in responses at all dose levels evaluated (150x106 [N=6], 300x106 [N=13], 450x106 [N=13], and 800x106 [N=3] CAR-T cells). The 450x106 CAR-T cell dose with the selected LD regimen is the recommended dose for expansion (RDE). Twelve BCMA-naïve r/r MM patients were treated with the RDE. The median follow-up for patients dosed with the RDE was 8.3 months, and the longest responding patient is in a stringent complete response (sCR) at 15 months post-infusion. As of the September 24, 2025, data cutoff date, the results for the 12-patient, BCMA-naïve cohort treated with the RDE were as follows:
- 92% (11/12) overall response rate (ORR)
- 75% (9/12) ≥complete response (CR) rate
- 91% (10/11 evaluable patients) achieved minimal residual disease (MRD) negativity (≤10-5)
- 7 of 12 patients remained on study as of the data cutoff date in ≥very good partial response (VGPR) 6 months or longer following receipt of a single dose of CB-011
CB-011 had a manageable safety profile across all dose levels and lymphodepletion regimens (N=48), with no cases of graft-versus-host disease (GvHD), immune effector cell-associated enterocolitis (IEC-EC), parkinsonism, or cranial nerve palsies. Treatment emergent adverse events (TEAEs) in ≥25% of all patients treated with CB-011 following the selected LD regimen (N=35) were as follows: neutropenia (80%), anemia (60%), thrombocytopenia (49%), infections (49%), dizziness (31%), cytokine release syndrome (31%), fatigue (31%), leukopenia (29%), decreased appetite (29%), constipation (26%), and pyrexia (26%). Notable adverse events in the RDE cohort included one CB-011-related grade 5 immune effector cell-associated hematotoxicity (ICAHT) on day 90, one grade 5 pneumonia not related to CB-011 on day 50, and one grade 4 CB-011-related Guillain-Barré Syndrome on day 129, which is resolving. In the cohort evaluating the 300x106 CAR-T cell dose level following the selected LD regimen, there was one grade 5 respiratory syncytial virus not related to CB-011 on day 73. Prophylactic measures for cytopenias and infections and early intervention for immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) have been successfully implemented in the protocol.
