CAR-M/Pembrolizumab Trial Doses First Patient With HER2-Overexpressing Solid Tumors


Initial data from the combination substudy are expected in the second half of 2023.

Carisma Therapeutics has dosed the first patient with HER2-overexpressing solid tumors in a phase 1 clinical trial (NCT04660929) assessing the combination of CT-0508 chimeric antigen receptor (CAR) macrophage (CAR-M) therapy with pembrolizumab (Keytruda; Merck).1

"We are excited by the progress being made on our CT-0508 clinical program with the dosing of the first patient in the combination study with KEYTRUDA®," Michael Klichinsky, PharmD, PhD, cofounder and chief scientific officer, Carisma Therapeutics, said in a statement.1 "The CT-0508 monotherapy trial has demonstrated early clinical validation of the CAR-M mechanism of action, and we are eager to explore this sub-study to assess the potential synergistic effect of CAR-M therapy in combination with KEYTRUDA®. The initiation of clinical manufacturing at Novartis' GMP cell therapy site is also a meaningful step forward in progressing our overarching manufacturing strategy, and demonstrates our desire to work alongside best-in-class companies."

The trial has been initiated at multiple site locations in the United States. It is a substudy of an ongoing, first-in-human trial evaluating the safety of CT-0508 alone in patients with solid tumors. Initial data from the substudyare expected in the second half of 2023.2

READ MORE: MUC16-Targeted Bispecific T-Cell Engager Cleared for Trial in Ovarian Cancer, Other Tumors

The most updated data from the parent trial were presented at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting in November 2022.3 CT-0508 was well-tolerated with no dose-limiting toxicities or major organ toxicities. Most adverse events (AEs) were grade 1 or 2, excepting 5 serious AEs - 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. Preliminary efficacy analysis demonstrated a best overall response of stable disease in 5 participants (55.6%). Data from Group 2 of the trial is expected in the second half of 2023.2

“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,” Klichinsky, said in an earlier statement.“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.”

1. Carisma Therapeutics announces first patient dosed in phase 1 study of CT-0508 in combination with KEYTRUDA® (pembrolizumab) in patients with HER2 overexpressing solid tumors. News release. June 28, 2023.
2. Carisma Therapeutics reports second quarter 2023 financial results and recent business highlights. News release. Carisma Therapeutics. August 10, 2023.
3. 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
4. Carisma Therapeutics announces clinical & pre-clinical updates. News release. Carisma Therapeutics. November 11, 2022.
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