Carisma’s CAR-Monocyte Fast Tracked for HER2-Overexpressing Solid Tumors
CT-0525 is being evaluated in a phase 1 clinical trial currently enrolling participants.
Eugene P. Kennedy, MD
Credit: Penn Center for Innovation
The FDA has granted Fast Track designation to Carisma Therapeutics’ chimeric antigen receptor-monocyte (CAR-M) cellular therapy CT-0525 for the potential treatment of solid tumors that overexpress human epidermal growth factor receptor 2 (HER2).1
"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, Carisma, said in a statement.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."
CT-0525 is being evaluated in a phase 1 clinical trial (NCT06254807). The trial is currently enrolling participants with unresectable or metastatic solid tumors overexpressing HER2 whose disease has progressed on standard approved therapies. The trial is set to have 2 dose escalation cohorts and is designed to assess the safety, tolerability, and manufacturing feasibility of CT-0525. The trial’s primary outcome measures are the frequency and severity of adverse events, including cytokine release syndrome, at 28 days after treatment, as well as assessing the feasibility of manufacturing CT-0525.
"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, said in a statement last year.2 "We look forward to the clinical development of CT-0525."
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Carisma received investigational new drug application clearance to initiate the phase 1 trial in December 2023 and at the time, estimated dosing the first patient in the first half of 2024.
"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, added.2 "Through this Phase 1 study, we aim to advance our understanding of safety, tolerability, manufacturing feasibility and mechanism of action of CT-0525."
CT-0525 is a first-in-class, ex vivo gene-modified autologous CAR-M cellular therapy. Carisma believes that this modality should address challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity.
Carisma previously presented preclinical data demonstrating feasibility of the CT-0525 approach and reduced tumor growth in multiple models of solid tumors. Anti-HER2 CAR mRNA/LNP led 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.3
"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," Klichinsky said in a previous statement about the preclinical data.3 "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."
