Study of CT-0525 Doses First Patient With a Solid Tumor Overexpressing HER2

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The first patient has been given CT-0525, a first-in-class, ex vivo gene-modified autologous CAR-monocyte cellular therapy, in a phase 1 trial of the agent for those with HER2-overexpressing solid tumors.

DNA Molecule: © Design Cells - stock.adobe.com

DNA Molecule: © Design Cells - stock.adobe.com

About the Phase 1 Study of CT-0525

Trial Name: An Open-Label, Single-Arm Study of Autologous Anti-HER2 Chimeric Antigen Receptor Monocytes (CT-0525), in Participants With HER2 Over Expressing Solid Tumors

ClinicalTrials.gov Identifier: NCT06254807

Sponsor: Carisma Therapeutics Inc.

Recruitment Contact: Jeanette Wetzel, 267-491-6544, jeanette.wetzel@carismatx.com

Completion Date: March 31, 2026

A phase 1 trial (NCT06254807) evaluating CT-0525 has dosed its first patient with a HER2-overexpressing solid tumor, according to Carisma Therapeutics Inc.1 This marks the first chimeric antigen receptor (CAR)-monocyte to be evaluated in humans in the solid tumor setting.

CT-0525, a first-in-class, ex vivo gene-modified autologous CAR-monocyte cellular therapy, is being developed for the treatment of solid tumors that overexpress HER2.

A CAR-monocyte may help combat some of the challenges associated with treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity. Specifically, CT-0525 shows promise in enabling significant dose escalation, bettering tumor infiltration, increasing persistence, and lessening manufacturing time vs that seen with macrophage therapy.

"Dosing of the first patient in the CT-0525 phase 1 trial is a significant step in the development of engineered myeloid cells, marking the first time a CAR-monocyte is tested in humans in the solid tumor setting," said Eugene P. Kennedy, MD, chief medical officer of Carisma, in a press release. "Our preclinical data leads us to believe that this next-generation approach of our CAR-M platform has the potential to have a greater impact on patients than our initial CAR-macrophage program, particularly through faster manufacturing, higher dosing, and increased potency, persistence, and tumor infiltration. We look forward to progressing this trial and expect to report initial data by the end of 2024."

Preclinical data of CT-0525 showed reduced tumor growth with the platform across multiple solid tumor models.2 In November 2023, the FDA cleared the investigational new drug application for CT-0525 for the treatment of HER2-overexpressing solid tumors, leading to the phase 1 study of the agent for this indication.

The open-label, single-arm study will evaluate the safety, tolerability, and manufacturing feasibility of CT-0525.1

Patients aged 18 years and older with locally advanced or metastatic solid tumors that overexpress HER2 and whose disease has progressed on standard approved therapies are eligible for enrollment in the study.2 Patients must also have at least 1 measurable lesion, an ECOG performance status of 0 to 1 at screening, adequate cardiac function, adequate hepatic function, and an O2 saturation > 85% to be enrolled.

The study will consist of 2 dose-escalation cohorts. Cohort 1 will include 3 patients who will be treated with a single intravenous (IV) administration of CT-0525 at a dose of 3 billion CAR-positive cells given on day 1. In cohort 2, 3 patients will be given a single IV administration of CT-0525 at 10 billion CAR-positive cells, also on day 1.

The primary end points of the study are to assess the safety and tolerability of CT-0525 by estimating the frequency and severity of adverse events in patients with HER2-overexpressing solid tumors and to evaluate the feasibility of manufacturing CT-0525.

The study is recruiting patients in Ohio and has an estimated study completion date of March 31, 2026. Initial data from the study are expected to be released by the end of 2024.

REFERENCES:
1. Carisma Therapeutics announces first patient dosed in phase 1 clinical trial of CT-0525, a novel HER2-targeting CAR-monocyte. News release. Carisma Therapeutics Inc. May 16, 2024. Accessed May 19, 2024. https://tinyurl.com/3m886ycz
2. Carisma Therapeutics announces FDA clearance of IND application for CT-0525, a novel HER2-targeting CAR-monocyte. News release. Carisma Therapeutics Inc. November 28, 2023. Accessed May 19, 2024. https://tinyurl.com/ycxkbfbt
3. CAR-monocytes for the treatment of HER2 overexpressing solid tumors. ClinicalTrial.gov. Updated April 11, 2024. Accessed May 19, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06254807
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