Abstract OT-28-06: A phase 1, first in human study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor in subjects with HER2 overexpressing solid tumors

Abstract

Abstract Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but not in those with solid tumors. Macrophages are actively recruited into and more abundantly present in the tumor microenvironment (TME) as compared to T cells. Tumor- associated macrophages (TAMs), typically evince immunosuppressive behavior, but when engineered to be proinflammatory, may be an ideal vector to administer adoptive cellular therapy in solid tumors. Furthermore, insertion of a CAR confers on the macrophages the ability to selectively recognize and phagocytose antigen overexpressing cancer cells. CAR macrophages can also potentially interact with, stimulate, and present neoantigens to T cells. Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in many cancers, including but not limited to breast and gastroesophageal cancers (Table 1). CT-0508 is a cell product comprised of autologous monocyte-derived pro-inflammatory macrophages expressing an anti-HER2 CAR. In vitro and in vivo studies have shown that CT-0508 leads to cancer cell phagocytosis sparing normal cells, decreased tumor burden and prolonged survival. CT-0508 cells were safe in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. This is a FIH Phase 1 study to evaluate safety, tolerability, cell manufacturing feasibility, trafficking, and preliminary evidence of efficacy of investigational product CT-0508 on approximately 18 subjects with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 who have failed available therapies including anti-HER2 therapies when indicated.Filgrastim, will be used to mobilize autologous hematopoietic progenitor cells for monocyte collection by apheresis. CT-0508 cell product will be manufactured, prepared and cryopreserved. Group 1 will receive CT-0508 infusion split over D1, 3 and 5. Subjects will be continually assessed for acute and cumulative toxicity. Dose limiting toxicities will be observed and addressed by a Safety Review Committee. Group 2 will receive the full CT-0508 infusion on D1. Pre and post treatment biopsies and blood samples will be collected to investigate correlates of trafficking, persistence, TME modulation, immune response and safety. Citation Format: Natalie Grover, Debora Barton, Amy Ronczka, Joshua Bauml. A phase 1, first in human study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor in subjects with HER2 overexpressing solid tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-28-06.