Abstract Details

I – Gene & Cell Therapy Trials in Progress -> Gene & Cell Therapy Trials in Progress

1550: A Phase 1, First in Human (FIH) Study of Autologous Anti-HER2 Chimeric Antigen Receptor Macrophage (CAR-M) in Participants (pt) with HER2 Overexpressing Solid Tumors

Type: Poster Session

Poster Board Number: 1550

Presentation Details

Session Title: Friday Poster Session
Location:
Start Time: 5/19/2023 12:00
End Time: 5/19/2023 14:00

Background: Macrophages are abundant in the solid tumor microenvironment (sTME) and can exhibit both pro- and anti-tumor functions. Macrophages can be redirected by CAR expression to phagocytose cancer cells in an antigen-specific manner. CAR-M can reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and anti-tumor immunity. CT-0508 is comprised of autologous monocyte-derived proinflammatory macrophages expressing an anti-HER2 CAR. Pre-clinical studies showed that CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden, prolonged survival, and was safe and effective. Notably, anti-HER2 CAR-M treatment led to activation of the sTME, with infiltration of CD8+ and CD4+ T cells, NK cells, dendritic cells, and increased activated CD8+ tumor infiltrating lymphocytes. In a pre-clinical model of advanced solid tumor resistant to PD1 blockade, mice treated with anti-HER2 CAR-M combined with a PD1 blocking antibody demonstrated improved tumor control, overall survival, and TME activation compared to either treatment alone, indicating synergy and capacity for CAR-M to sensitize solid tumors to checkpoint blockade. Methods: This Phase 1, FIH study is evaluating safety, tolerability, cell manufacturing feasibility, trafficking, TME activation, and preliminary evidence of efficacy of investigational product CT-0508 in 18 pt with locally advanced (unresectable) /metastatic solid tumors overexpressing HER2. Pt previously treated with anti-HER2 therapies are eligible. Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation. Group 1 pt (n = 9; enrollment complete) received fractionated doses over Days 1, 3, and 5. Group 2 pt (n = 9) receive CT-0508 as a single infusion on D1. Additional cohorts include: CT-0508 co-administered with pembrolizumab and CT-0508 monotherapy administered intraperitoneally in pt with peritoneal predominant disease. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety (immunogenicity), trafficking (qPCR, RNA in situ hybridization), CT-0508 persistence in blood and tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others.

Joanne Mortimer¹, Yara Abdou², E. Claire Dees², Naoto Ueno³, Melissa Johnson⁴, Richard T. Maziarz⁵, Jennifer Specht⁶, Yuan Yuan⁷, Paula Pohlmann⁸, Mathew Angelos⁹, Saar Gill¹⁰, Amy Ronczka¹¹, Thomas Condamine¹¹, Dan Cushing¹¹, Michael Klichinsky¹¹, Debora Barton¹¹, Ramona Swaby¹¹, Kim ReissBinder<sup>9

1</sup>City of Hope, Duarte, CA,²University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC,³University of Hawaii, Honolulu, HI,⁴Sarah Cannon Research Institute, Nashville, TN,⁵Oregon Health & Science University, Portland, OR,⁶Fred Hutchinson Cancer Center, Seattle, WA,⁷Cedars Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA,⁸The University of Texas M.D. Anderson Cancer Center, Houston, TX,⁹University of Pennsylvania Abramson Cancer Center, Philadelphia, PA,¹⁰University of Pennsylvania Abramson Cancer Center,, Philadelphia, PA,¹¹Carisma Therapeutics, Philadelphia, PA
 J. Mortimer: None.