CAR Macrophage Therapy Continues to be Well-Tolerated in Solid Tumors

Carisma Therapeutics’ chimeric antigen receptor (CAR) macrophage CT-0508 has continued to be well-tolerated in patients with solid tumors, with promising signs of efficacy, according to updated data from a phase 1, first-in-human trial (NCT04660929).1 Data from the trial were presented at the at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois by Kim A. Reiss Binder, MD, assistant program director, Hematology/Oncology Fellowship Program, and assistant professor of medicine, University of Pennsylvania Hospital, and also during a company webcast.1,2 CGTLive previously spoke with Binder to learn more about the first-in-human trial of CT-0508. "CAR macrophages do not require chemotherapy conditioning, CT-0508 does not cause severe cytokine release syndrome (CRS) or neurotoxicity. Macrophages do not cause graft versus host disease as they don't have T-cell receptors and macrophages can thus be used as an allogeneic off-the-shelf product. There is potential for epigenetic compatibility, and importantly, macrophages do not cause immunosuppression,” Michael Klichinsky, PharmD, PhD, said during a company webcast.1 “From a mechanism of action point of view, CAR macrophages infiltrate solid tumors by using viral vectors with durable transduction. We see durable CAR expression; we see direct cytotoxicity through phagocytosis and other means. We see the CAR macrophages are able to remodel the TME, recruit T-cells and present antigen, lead to epitope spreading, and can sensitize checkpoint inhibitor-resistant tumors to immunotherapy.” New data presented demonstrated a favorable safety and tolerability profile in the first 7 patients treated. Patients had tumors including breast cancer, gastrointestinal tumors, ovarian cancer, and salivary duct carcinoma and were heavily pretreated, with a median number of 3 prior therapies, ranging to 11. READ MORE: CAR Macrophage Therapy for HER2 Solid Tumors Continues Through First in Human Trial Investigators found that in these patients, there have been no dose-limiting toxicities. Five patients had grade 1 or 2 CRS and no cases of Immune effector cell-associated neurotoxicity syndrome have been observed. One patient experienced serious adverse events (SAE) of CRS and an infusion reaction which resolved within 24 hours. Two patients had SAEs relating to progression of disease. Overall, AEs were mostly mild and included laboratory abnormalities and there were no major organ toxicities. Investigators assessed preliminary efficacy and found that 4 of 7 patients had stable disease at 8 weeks. “Car macrophages demonstrate feasible manufacturing. The process is largely automated, the cells can be cryopreserved and in fact are stable in a cryopreserved state for very long periods of time. The process is fairly rapid for an autologous program. Our manufacturing cycle takes 7 days with the majority of the time being hands off. This process allows for reduced cost of goods,” Klichinsky added.1 Carisma also shared that the first cohort has completed accrual and the second cohort is now enrolling. CT-0508 received fast track designation for the treatment of solid tumors in September 2021.3 REFERENCES 1. Carisma Therapeutics to Host Webcast on Phase 1 Clinical Trial of Engineered Macrophage Therapy. News release. Carisma Therapeutics. June 17, 2022. https://carismatx.com/carisma-therapeutics-to-host-webcast-on-phase-1-clinical-trial-of-engineered-macrophage-therapy/ 2. Reiss KA, Yuan Y, Ueno NT, et al. A phase 1, first-in-human (FIH) study of the anti-HER2 CAR macrophage CT-0508 in subjects with HER2 overexpressing solid tumors. Presented at: 2022 ASCO Meeting, June 3-7; Chicago, IL. Abstract # 2533 3. CARISMA Therapeutics announces US Food and Drug Administration grants fast track designation to CT-0508 for the treatment of patients with solid tumors. News release. CARISMA Therapeutics, Inc. September 22, 2021. Accessed May 17, 2022. https://carismatx.com/carisma-therapeutics-announces-u-s-food-and-drug-administration-grants-fast-track-designation-to-ct-0508-for-the-treatment-of-patients-with-solid-tumors/