CAR Macrophage Therapy for HER2 Solid Tumors Continues Through First in Human Trial
Investigators are evaluating the safety, tolerability and preliminary efficacy of CT-0508 in patients with solid tumors and HER2 overexpression.
In a phase 1, first-in-human study, investigators are evaluating the safety, tolerability and preliminary efficacy of an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) macrophage therapy, CT-0508 (Carisma Therapeutics), in participants with solid tumors and HER2 overexpression.1
A brief outline of the trial and the investigational therapy were presented by Yara Abdou, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, at the 2022 American Society of Gene and Cell Therapy Annual Meeting, taking place May 16-19, 2022 in Washington, DC.
“Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but with less success in those with solid tumors,” the investigators reported.
Since macrophages are abundant in the solid tumor microenvironment, it has been hypothesized that they can be engineered to be proinflammatory, serving as an ideal vector for adoptive solid tumor cellular therapy. Insertion of a CAR on the macrophages allows them to recognize and ingest antigen-overexpressing cancer cells, reprogram the solid tumor microenvironment, and present neoantigens to T cells, resulting in epitope spreading and improved immune memory. Meanwhile, HER2 overexpression is known to promote tumorigenesis in many solid tumors, notably in bladder, gastric, breast and ovarian tumors.
CT-0508 comprises autologous monocyte-derived proinflammatory macrophages expressing an anti-HER2 CAR. In pre-clinical studies, CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden, prolonged survival, and was safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. In September 2021, the FDA granted a fast-track designation to CT-0508 for use as a potential therapeutic option for patients with solid tumors.2
The study, which is also evaluating the cell manufacturing feasibility and trafficking, will include 18 participants with locally advanced or metastatic solid tumors overexpressing HER2, with progression on available therapies. Group 1 participants will receive CT-0508 infusion split over day 1, 3 and 5, while those in group 2 will receive the full CT-0508 infusion on day 1. The researchers will collect pre and post treatment biopsies and blood samples to investigate correlates of safety, trafficking, CT-0508 persistence in blood and in the tumor, target antigen engagement and tumor microenvironment modulation immune response.
In November 2021, Carisma Therapeutics presented preliminary findings from the trial, demonstrating that CT-0508 was well tolerated after infusion, with no dose limiting toxicities. “We will continue to enroll patients in the landmark clinical trial of CT-0508,” said Debora Barton, MD, chief medical officer at Carisma Therapeutics, at that time.3
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