A first-in-human phase 1, multicenter, open-label study of CB-011, a next-generation CRISPR-genome edited allogeneic anti-BCMA immune-cloaked CAR-T cell therapy, in patients with relapsed/refractory multiple myeloma (CAMMOUFLAGE trial).

• DOI: 10.1200/jco.2023.41.16_suppl.tps8063
• Publication Date: 2023-06-04T16:11:56Z
• Authors: Jesus G. Berdeja; Thomas G. Martin; Adriana Rossi; James H. Essell; David Samuel DiCa...; Sham Mailankody; Neeraj Saini; Houston Holmes; Binod Dhakal; Cristina J. Gaspa...; Samir S. Parekh; Socorro Portella; Guy Ledergor; Ashley Hammad; Franco Davi; Justin Skoble; Elizabeth Garner; Steven Brian Kanner; Syed Rizvi; Sundar Jagannath
• Keywords: Cell therapy

TPS8063 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 may inherent challenges, including functional deficiencies patient’s T cells, that could yield an inconsistent or impaired product, as well require extended time and complexity manufacturing, thereby limiting patient access potentially requiring bridging therapy. CB-011 is allogeneic, off-the-shelf anti-BCMA therapy derived from healthy donor 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 generate 4 genome edits manufacture CB-011: (i) TRAC gene knocked out eliminate receptor (TCR) expression prevent graft versus host disease (GvHD), (ii) BCMA-specific CAR site-specifically inserted into locus random integration serves target tumor antigen, (iii) B2M HLA class I molecules mitigate cytotoxicity, (iv) a B2M-HLA-E fusion transgene overcome NK cell-mediated killing following recognition “missing self.” This immune cloaking strategy has potential allow persistent antitumor activity cells context antigen engagement. Significant preclinical efficacy vitro vivo supports clinical evaluation CB-011. Methods: being evaluated multicenter, Phase 1 trial patients r/r MM. 3+3 dose escalation design followed by expansion maximum tolerated (MTD) and/or recommended 2 (RP2D) utilized. Primary objectives are determine safety tolerability CB-011, (RP2D). Additional key include preliminary pharmacokinetics (PK). After concurrently receiving lymphodepletion cyclophosphamide (300 mg/m /d) fludarabine (30 for 3 days, receive single infusion efficacy. Antitumor response measured International Myeloma Working Group criteria. The CaMMouflage actively enrolling additional information available on clinicaltrials.gov (NCT05722418). Clinical information: NCT05722418 .