Background: Autologous CAR-T cell therapies have shown significant benefit in the treatment of adults with relapsed/refractory multiple myeloma (r/r MM). However, these CAR-T cell therapies may have inherent challenges, including functional deficiencies in the patient’s T cells, that could yield an inconsistent or impaired product, as well as require extended time and complexity in manufacturing, thereby limiting patient access and potentially requiring bridging therapy. CB-011 is an allogeneic, off-the-shelf anti-BCMA CAR-T cell therapy derived from healthy donor T cells. A next-generation CRISPR-Cas12a genome-editing technology using CRISPR hybrid RNA-DNA (chRDNA) guides, developed at Caribou to significantly reduce off-target editing, was implemented to generate 4 genome edits in the manufacture of CB-011: (i) the TRAC gene was knocked out to eliminate T cell receptor (TCR) expression and prevent graft versus host disease (GvHD), (ii) the BCMA-specific CAR was site-specifically inserted into the genome at the TRAC locus to eliminate random integration and serves to target the tumor antigen, (iii) the B2M gene was knocked out to eliminate expression of HLA class I molecules to mitigate host T cell cytotoxicity, and (iv) a B2M-HLA-E fusion transgene was site-specifically inserted into the genome at the B2M locus to overcome host NK cell-mediated killing following recognition of “missing self.” This immune cloaking strategy has the potential to allow persistent antitumor activity of the CAR-T cells in the context of antigen engagement. Significant preclinical efficacy in vitro and in vivo supports the clinical evaluation of CB-011. Methods: CB-011 is being evaluated in a multicenter, Phase 1 clinical trial in patients with r/r MM. A 3+3 dose escalation design followed by expansion at the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) is being utilized. Primary objectives are to determine the safety and tolerability of CB-011, and the recommended Phase 2 dose (RP2D). Additional key objectives include preliminary antitumor activity and pharmacokinetics (PK). After concurrently receiving lymphodepletion therapy with cyclophosphamide (300 mg/m²/d) and fludarabine (30 mg/m²/d) for 3 days, patients receive a single dose infusion of CB-011 and are followed for safety and efficacy. Antitumor activity and disease response are measured by International Myeloma Working Group criteria. The CaMMouflage Phase 1 trial is actively enrolling patients and additional information is available on clinicaltrials.gov (NCT05722418). Clinical trial information: NCT05722418.