A first-in-human phase 1, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify).

• DOI: 10.1200/jco.2024.42.16_suppl.tps6586
• Publication Date: 2024-06-10T18:35:41Z
• Authors: Naval Guastad Daver; Abhishek Maiti; David Andrew Sallman; Gail J. Roboz; Melhem M. Solh; Filippo Milano; Stephen Anthony S...; Alireza Eghtedar; Steven Brian Kanner; Guy Ledergor; Donna Marcy; Elizabeth Garner; Brian J. Francica; McKay Shaw; Kalin Bird; Jennifer Rattan; Enrique Zudaire; Socorro Portella; Pankit Vachhani; Jae H. Park
• Keywords: Refractory (planetary science); Open label

TPS6586 Background: CAR-T cell therapies have shown significant clinical benefit in treating adults with many hematologic malignancies. In acute myeloid leukemia (AML), a challenge the development of has been limitation suitable target antigens since are also expressed on hematopoietic stem cells (HSCs). The antigen C-type lectin-like molecule-1 (CLL-1) emerged as an attractive therapeutic due to its expression AML mature blasts and leukemic absence HSCs. CB-012 is allogeneic therapy that targets CLL-1. derived from healthy donor T by using Cas12a CRISPR hybrid RNA-DNA (chRDNA) technology introduce 5 genome edits: (1) TRAC gene knockout (KO), which eliminates receptor reduce risk graft-versus-host disease, (2) site-directed insertion fully human anti-CLL-1 CAR into locus, (3) KO PD-1 enhance antitumor activity reducing exhaustion, (4) β2-microgobulin ( B 2M) KO, HLA class I presentation mitigate host cell-mediated rejection, (5) B2M–HLA-E-peptide fusion 2M locus NK rejection. murine xenograft models AML, significantly reduced tumor burden increased survival mice bearing CLL-1 + PD-L1 tumors. Methods: being evaluated multicenter, Phase 1 trial patients relapsed/refractory (r/r) AML. A 3+3 dose escalation design utilized primary objectives determine safety tolerability recommended 2 (RP2D). An expansion phase will follow at dose(s) for expansion. Additional include preliminary pharmacokinetics. Key inclusion criteria nonproliferative disease defined ≤25% bone marrow peripheral blood, ECOG performance status ≤1, adequate organ function. After receiving lymphodepletion cyclophosphamide (750 mg/m /d) fludarabine (30 administered concurrently 3 days followed 2-day break, receive single-dose infusion efficacy. portion study actively enrolling patients. AMpLify registered clinicaltrials.gov (NCT06128044). Clinical information: NCT06128044 .