Abstract CT232: Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*)

Background: CAR-T cell therapy targeting CD19 results in marked tumor regression for patients (pts) with B-cell malignancies. It would be ideal to extend the success of CAR-T cell therapy to common epithelial cancers. MUC1* is a post-translationally modified/cleaved form of mucin 1 (MUC1) that is frequently expressed on breast tumors, functions as a growth factor receptor, and is a novel antigen for CAR-T cell therapy. Minerva Biotechnologies developed a CAR (huMNC2-CAR44) that specifically recognizes MUC1* and does not bind to full-length MUC1 or MUC1* negative cells. huMNC2-CAR44 product consists of autologous T cells transduced with a proprietary lentiviral vector encoding humanized MNC2-scFv (MUC1* targeting head), CD8 α; leader, hinge and transmembrane domains, 4-1BB, and CD3ζ domains. Methods: NCT04020575 is a phase I study evaluating the safety of adoptively transferred autologous T cells genetically modified to express huMNC2-CAR44 in pts with metastatic breast cancer (MBC). Key eligibility criteria: MBC of known ER, PR and HER2 status which has MUC1* membrane expression ≥30% by IHC, measurable or evaluable disease, receipt of standard systemic therapies known to confer benefit, age \u003e18, informed consent, adequate organ function, and KPS ≥60%. Key exclusions: active autoimmune disease or uncontrolled infection, contraindication to cyclophosphamide, anticipated survival 17%. Once the MTD has been determined, up to 15 more patients will be enrolled in each of 3 expansion cohorts (Luminal, HER2 positive, and TNBC) to explore the anti-tumor activity in these patient populations and to inform future huMNC2-CAR44 T cell trials. Study is open to enrollment. Citation Format: Jennifer M. Specht, David Maloney, Robert Pierce, Monica Dherin, Susan Ra, Quan V. Wu, Cynthia Bamdad. Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT232.