Meanwhile, the company’s lead CAR Macrophage candidate CT-0508, continues to show efficacy in multiple solid tumor trials.
The FDA has cleared Carisma Therapeutics' investigational new drug (IND) application for evaluating CT-0525 chimeric antigen receptor (CAR) monocyte therapy in patients with solid tumors.1
"Clearance of the IND for CT-0525 is a significant milestone in Carisma's mission to develop innovative myeloid cell therapies for metastatic solid tumors," Steven Kelly, president and chief executive officer, Carisma, said in a statement.1 "Through this Phase 1 study, we aim to advance our understanding of safety, tolerability, manufacturing feasibility and mechanism of action of CT-0525."
Following the Study May Proceed notification from the FDA, Carisma expects to initiate a Phase 1 study in the coming months and to treat the first patient in the first half of 2024. The trial will assess the safety, tolerability, and the manufacturing feasibility of CT-0525 in participants with unresectable or metastatic HER2-overexpressing solid tumors whose disease has progressed on standard approved therapies. The trial will have 2 cohorts; participants in the first cohort will receive up to 3 billion CAR-positive cells intravenously and participants in the second cohort will receive up to 10 billion CAR-positive cells intravenously.
CT-0525 is an ex vivo gene-modified autologous cell therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). Carisma stated that their approach should address challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity.
"CT-0525 is the first CAR-Monocyte to be evaluated in the solid tumor setting. With a CAR-Monocyte's in vivo persistence, ability to differentiate into pro-inflammatory CAR macrophages, and multi-modal anti-tumor mechanism of action, along with its high cell yield, CT-0525 has the potential to improve the treatment paradigm for patients with HER2 overexpressing metastatic solid tumors," Michael Klichinsky, PharmD, PhD, cofounder and chief scientific officer, Carisma, added.1 "We look forward to the clinical development of CT-0525."
Previous preclinical data presented at the Society for Immunotherapy of Cancer’s (SITC) 2022 meeting demonstrated feasibility of the CT-0525 approach and showed reduced tumor growth in multiple models of solid tumors. Anti-HER2 CAR mRNA/LNP lead to a robust reduction in tumor burden over time in a CD34+ humanized NSG-S mouse model of lung cancer that overexpressed HER2. Meanwhile, mice that received administration of control mRNA did not experience a reduction in tumor burden. Systemic administration of CAR mRNA/LNP compared to systemic administration of control mRNA also showed a reduction in tumor burden over time. In the same mouse model, it was also found that CAR mRNA/LNP delivered intravenously reduced lung metastasis and cleared liver metastasis.2
"The data presented at SITC is incredibly exciting as it demonstrates that we have the ability to make CAR-M directly in vivo with mRNA/LNP technology, leading to robust and targeted antitumor activity," Michael Klichinsky, PharmD, PhD, the co-founder and chief scientific officer of Carisma, said in a statement released prior to the presentation.2 "This off-the-shelf approach to treat cancer with engineered myeloid cells, developed in collaboration with Moderna, has the potential to transform the CAR field and be applied to numerous cancer targets and indications."