FDA Awards Fast Track Designation to CT-0525 for HER2-Overexpressing Solid Tumors

The FDA has granted fast track designation to the ex vivo gene-modified autologous CAR-monocyte therapy, CT-0525, for use as a potential therapeutic option in patients with HER2-overexpressing solid tumors.¹

CT-0525 is based on CD14-positive monocytes that were engineered with an Ad5f35 adenoviral vector to express an anti-HER2 CAR.2 Preclinical data have showcased the feasibility, phenotype, pharmacokinetics, durable CAR expression, cellular fate, antigen specificity, and activity of the therapy. Compared with macrophage therapy, the CAR-Monocyte approach may allow for significant dose escalation, strengthen tumor infiltration, boost persistence, and cut manufacturing time, according to Carisma Therapeutics, Inc., the drug developer.

The safety and tolerability, as well as the manufacturing feasibility, of the therapy will be investigated in patients with locally advanced or metastatic solid tumors and HER2 overexpression who have progressed on standard approved therapies as part of an open-label, single-arm, phase 1 study (NCT06254807).³ The trial is currently recruiting.

“Receiving fast track designation for CT-0525 from the FDA marks a significant milestone for Carisma, highlighting the FDA’s recognition of the serious and life-threatening nature of these malignancies and the potential of CT-0525 to meet this critical medical need,” Eugene P. Kennedy, MD, chief medical officer of Carisma Therapeutics, Inc., stated in a news release.¹ “We are committed to working closely with the FDA to accelerate the development of CT-0525. Currently we are enrolling patients in the phase 1 clinical trial and remain on track to report initial clinical data by the end of 2024.”

The study will enroll patients who are at least 18 years of age, have at least 1 measurable lesion by RECIST 1.1 criteria, an ECOG performance status of 0 or 1 at the time of screening, and good organ function.³ They must be willing to undergo serial biopsies and they cannot have concurrent infections.

Six or more patients with HER2+/3+ solid tumors will first undergo granulocyte colony–stimulating factor mobilization and apheresis, CAR-Monocyte manufacturing, bridging therapy, and baseline staging. They will be split into two cohorts; cohort 1 will receive the therapy at 3 x 10⁹ CAR-positive cells and cohort 2 will receive the therapy at 10 x 10⁹ CAR-positive cells on day 1 (n = ≥3, each).

The primary objective of the study is to examine the safety and tolerability of CT-0525 in this population, as well as to evaluate the feasibility of manufacturing the product. Secondary objectives include characterizing the in vivo cellular kinetics profile of CT-0525 transgene into peripheral blood and target tissues, and to estimate the objective response rate and duration of response with the therapy. Exploratory end points include estimation of progression-free survival and overall survival with the product.

The study is enrolling at participating clinical sites throughout the United States, including UNC Lineberger Comprehensive Cancer Center, the University of Texas MD Anderson Cancer Center, Oregon Health & Science University Knight Cancer Institute, Mayo Clinic Comprehensive Cancer Center, Cedars Sinai in Los Angeles, Roswell Park Comprehensive Cancer Center, University of Pennsylvania Abramson Cancer Center, Cleveland Clinic Cancer Center, and the University of Cincinnati Cancer Center.

References

1. Carisma Therapeutics granted FDA fast track designation for CT-0525 for the treatment of HER2-overexpressing solid tumors. News release. Carisma Therapeutics, Inc. June 25, 2024. Accessed July 12, 2024. https://www.prnewswire.com/news-releases/carisma-therapeutics-granted-fda-fast-track-designation-for-ct-0525-for-the-treatment-of-her2overexpressing-solid-tumors-302180804.html
2. Abdou Y, Pohlmann PR, Maziarz RT, et al. A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2-overexpressing solid tumors. J Clin Oncol. 2024;42(suppl 16):TPS2682. doi:10.1200/JCO.2024.42.16_suppl.TPS2682
3. CAR-monocytes for the treatment of HER2 overexpressing solid tumors. ClinicalTrials.gov. Updated April 11, 2024. Accessed July 12, 2024. https://clinicaltrials.gov/study/NCT06254807