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
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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.4 “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.”
