CAR-monocytes for HER2 Positive Cancer

Overseen By Daniel Cushing

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Carisma Therapeutics Inc

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CT-0525, a type of CAR-monocyte therapy, for individuals with HER2-positive cancers unresponsive to standard treatments. Researchers aim to determine if CT-0525 is safe and can be successfully manufactured for treating these advanced cancers. The trial includes two groups, each receiving different doses of the treatment through a single IV infusion. Individuals with HER2-positive tumors who have tried at least two other treatments without success may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) before starting. You must stop cytotoxic chemotherapy, tyrosine kinase inhibitors, and radiation therapy for 2 weeks, and biologic therapy for 4 weeks before joining. Check with the trial team about other medications you are taking.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that CT-0525, a new treatment, is undergoing its first safety test in humans. Earlier studies, which did not involve people, indicated it might reduce tumor growth in various cancers. As this is the initial human trial, the primary goal is to assess how well participants tolerate the treatment and identify any side effects. This Phase 1 trial marks the first step in evaluating CT-0525's safety for humans. Although detailed safety information from human studies is not yet available, the FDA has granted CT-0525 Fast Track status, indicating optimism about its potential benefits and safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for HER2-positive cancer, such as targeted therapies like trastuzumab and chemotherapy, CT-0525 represents a novel approach using CAR-monocytes. This treatment is unique because it harnesses genetically modified monocytes, a type of white blood cell, to specifically target and attack cancer cells that express the HER2 protein. Researchers are excited about CT-0525 because it offers a new mechanism of action, potentially providing a more precise and effective way to eliminate cancer cells while minimizing damage to healthy tissue. Additionally, the single IV administration on Day 1 offers a streamlined and potentially less burdensome treatment option for patients.

What evidence suggests that CT-0525 might be an effective treatment for HER2 positive cancer?

Research has shown that CT-0525, a new treatment, may help treat certain solid tumors with high levels of the HER2 protein. In early studies, these specially designed cells successfully shrank tumors and strengthened the body's immune system to fight cancer more effectively. The treatment targets the HER2 protein, abundant on some cancer cells, and helps the immune system attack those cells. Due to these promising results, the FDA has granted CT-0525 Fast Track designation, indicating its potential importance for patients with limited treatment options.

In this trial, participants will be divided into two cohorts to receive different dosages of CT-0525. Cohort 1 will receive a single IV administration of 3 billion CAR-positive cells, while Cohort 2 will receive 10 billion CAR-positive cells. ^{2 3 4 6 7}

Who Is on the Research Team?

Daniel Cushing

Principal Investigator

Carisma Therapeutics Inc

Are You a Good Fit for This Trial?

This trial is for people with advanced or metastatic solid tumors that have high levels of HER2 and who haven't responded to standard treatments. Specific details about who can join are not provided, but typically participants need to meet certain health standards.

Inclusion Criteria

Must have at least one measurable lesion according to RECIST v1.1

Must have an O2 saturation > 85%

My cancer has returned or spread, tests positive for HER2, and cannot be cured with treatment.

Exclusion Criteria

Known allergy or hypersensitivity to specific medications

Pregnant or lactating women

Active hepatitis B or hepatitis C infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV administration of CT-0525 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CT-0525

Trial Overview The study is testing a new treatment called CT-0525, which involves CAR-monocytes targeting the HER2 protein on cancer cells. It's an early-phase trial assessing safety, how well patients tolerate the treatment, and if it can be made reliably.

How Is the Trial Designed?

Group I: CT-0525 Experimental Treatment 1 Intervention

Cohort 1: 3 participants will be treated with a single IV administration of CT-0525 (3 billion CAR positive cells) on Day 1. Cohort 2: 3 participants will be treated with a single IV administration of CT-0525 (10 billion CAR positive cells) on Day 1.

Who Is Running the Clinical Trial?

Carisma Therapeutics Inc

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

The study successfully developed CAR-T cells that target the ERBB2 antigen, which is overexpressed in aggressive breast cancer cells, demonstrating increased apoptosis in the SKBR3 breast cancer cell line when co-cultured with these engineered T-cells.

This approach shows promise as a universal immunotherapy by enhancing T-cell activation and cytotoxicity without relying on traditional immune recognition mechanisms, suggesting potential for effective treatment of ERBB2-positive breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. Munisvaradass, R., Kumar, S., Govindasamy, C., et al.[2018]

CAR-T cells targeting HER2 can cause significant off-tumor toxicities in a mouse model, with the severity of these toxicities being influenced by the type of co-stimulatory domain used, particularly CD28, which was found to be the most toxic.

The study identified that CD4+ CAR-T cells are the main contributors to these toxicities, and variations in donor T cell sources can further affect the toxicity profile, suggesting that both intrinsic CAR-T cell characteristics and donor-specific factors play a role in the safety of CAR-T therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity. Hammill, JA., Kwiecien, JM., Dvorkin-Gheva, A., et al.[2020]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

HER2 CAR-engineered natural killer (NK) cells significantly enhance anti-tumor activity against HER2-expressing cancer cells, showing greater cytotoxicity than traditional CAR-T cells, especially in solid tumors.

Unlike CAR-T cells, HER2 CAR-NK cells do not cause harmful effects on non-cancerous cells, making them a safer option for immunotherapy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors. Portillo, AL., Hogg, R., Poznanski, SM., et al.[2021]

CAR-engineered NK-92 cells targeting the ErbB2 antigen showed effective tumor cell killing in laboratory tests and maintained their antitumor activity in live models, indicating their potential for cancer treatment.

Using γ-irradiation as a safety measure can prevent the replication of these NK cells while still allowing them to effectively attack tumors, making them a promising candidate for clinical use in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Schönfeld, K., Sahm, C., Zhang, C., et al.[2021]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06254807

Study Details | NCT06254807 | CAR-monocytes for the ... This is a first-in-human open-label study to evaluate the safety and tolerability, and manufacturing feasibility of anti-HER2 CAR-monocytes (CT-0525) in ...

2. onclive.com onclive.com/view/fda-awards-fast-track-designation-to-ct-0525-for-her2-overexpressing-solid-tumors

FDA Awards Fast Track Designation to CT-0525 for HER2- ... CT-0525 is an anti-HER2 CAR-monocyte therapy showing promising preclinical results in HER2-overexpressing solid tumors. The phase 1 study will ...

3. targetedonc.com targetedonc.com/view/study-of-ct-0525-doses-first-patient-with-a-solid-tumor-overexpressing-her2

Study of CT-0525 Doses First Patient With a Solid Tumor ... A phase 1 trial (NCT06254807) evaluating CT-0525 has dosed its first patient with a HER2-overexpressing solid tumor, according to Carisma Therapeutics Inc.

4. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P2-12-17/754071/Abstract-P2-12-17-A-Phase-1-First-in-Human-study

A Phase 1, First-in-Human study of autologous monocytes ... The 1st cohort of pts will receive 3 x 109 CT-0525 CAR positive monocytes administered in one infusion intravenously. If tolerated as per ...

5. nature.com nature.com/articles/s41467-024-55770-1

Chimeric antigen receptor macrophages (CAR-M) sensitize ... In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer ( ...

6. ir.carismatx.com ir.carismatx.com/news-releases/news-release-details/carisma-therapeutics-granted-fda-fast-track-designation-ct-0525

Carisma Therapeutics Granted FDA Fast Track Designation ... The Phase 1 clinical trial for CT-0525 is an open-label study designed to assess the safety, tolerability, and manufacturing feasibility of CT- ...

7. synapse.patsnap.com synapse.patsnap.com/article/fda-accelerates-carisma-cell-therapy-for-solid-tumors

FDA Accelerates Carisma Cell Therapy for Solid Tumors Presently, CT-0525 is in phase 1 of clinical trials, with results anticipated later this year. The trial involves patients with advanced or ...