CT-0508 Demonstrates Cytotoxicity in Solid Tumors

CT-0508, Carisma Therapeutics’ chimeric antigen receptor macrophage (CAR-M) therapy demonstrated safety, feasibility, and clinical validation of its mechanism of action in HER2-overexpressing solid tumors in updated data from a phase 1, first-in-human study (NCT04660929).¹

These data were presented at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, November 8-12, 2022, in Boston, Massachusetts, by Kim A. Reiss Binder, MD, assistant professor of medicine, University of Pennsylvania Hospital.1

“In preclinical studies, CAR-M phagocytose tumor cells, activate the tumor microenvironment (TME), recruit T cells, and induce antitumor T cell immunity. CT-0508 is a first-in-class CAR-M, comprised of autologous monocyte derived macrophages expressing an anti-HER2 CAR,” Reiss said during her presentation.¹

The trial has dosed 9 participants with breast (n = 4), esophageal (n = 2), choloangiocarcinoma (n = 1), ovarian (n = 1), and salivary carcinoma (n = 1) cancer. Participants had a median age of 58 years (range, 45-73); 3 (33.3%) were male, and all were White. Participants had a median of 3 prior therapies (range, 2-11) and a median of 2 prior anti-HER2 therapies (range, 0-9). Five participants (55.6%) had also received prior radiotherapy.

WATCH NOW: Kim A. Reiss Binder, MD, on the Potential of CAR Macrophages in Solid Tumors

Reiss and colleagues found that CT-0508 was well-tolerated with no dose-limiting toxicities or major organ toxicities. Most adverse events (AEs) were grade 1 or 2, although there were 5 serious AEs that did occur. These included 2 cases of cytokine release syndrome and 1 infusion reaction deemed related to treatment as well as 1 case of gastrointestinal hemorrhage and 1 case of worsening dyspnea related to progressive disease. No AEs led to study discontinuation or CT-0508 dose modification. The investigators also explored preliminary efficacy and determined a best overall response of stable disease in 5 participants (55.6%).

“The data from Group 1 of our first-in-human CAR-M clinical trial provides evidence that CAR-M therapy is feasible and generally well-tolerated by patients with certain late-stage metastatic cancers,” Michael Klichinsky, PharmD, PhD, cofounder and chief scientific officer, Carisma Therapeutics, said in a statement.² “The translational data collected from these patients is highly encouraging. We look forward to advancing CT-0508 into Group 2 of the monotherapy safety trial, as well as in a combination sub-study with the T cell checkpoint inhibitor pembrolizumab.”

Biomarker studies were also conducted and revealed transient elevations of pro-inflammatory cytokines, which resolved within 48 hours.¹ RNAscope technology confirmed rapid migration out of the blood within 4 to 8 hours and into the TME in 8 participants. Biopsies revealed activation of the TME in 6 participants as well as increased T cell clonality. These clones were found to be cytotoxic within the TME.

“CT-0508 led to increased T-cell clonality and significant expansion of newly emergent T cell clones within the TME with concomitant CD8 T cell activation, demonstrating induction of anti-tumor immunity,” Reiss concluded her presentation.¹

Click here to view more coverage of the 2022 SITC meeting.

REFERENCES

1. Reiss KA, Yuan Y, Ueno NT, et al. A phase 1, first-in-human (FIH) clinical trial of the anti-HER2 CAR macrophage CT-0508 in participants with HER2 overexpressing solid tumors.Presented at: SITC 37th Annual Meeting, November 8012, 2022, in Boston, Massachusetts. Poster #634
2. Carisma Therapeutics announces clinical & pre-clinical updates. News release. Carisma Therapeutics. November 11, 2022. https://carismatx.com/carisma-therapeutics-announces-clinical-pre-clinical-updates/