CAR-Macrophages + Pembrolizumab for HER2 Positive Cancer

Not currently recruiting at 6 trial locations

Overseen By Ramona Swaby, MD, Vice President - Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Carisma Therapeutics Inc

Must not be taking: Corticosteroids, Immunosuppressants

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR-macrophages, a type of cell therapy, for individuals with HER2-positive cancers, often including certain breast and stomach cancers. The goal is to assess the safety and effectiveness of this treatment both alone and in combination with Pembrolizumab. Participants are divided into groups receiving varying doses of the treatment through different methods. This trial may suit those with HER2-positive tumors who have not found success with other treatments. Participants must be willing to undergo a tumor biopsy and have sufficient energy for daily activities. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CAR-macrophages, specifically the CT-0508 therapy, have a safe and manageable safety profile in early studies. This treatment proved safe for patients with tumors exhibiting high levels of HER2. Serious side effects were uncommon, and patients generally tolerated the treatment well.

When combined with pembrolizumab, a treatment already approved for some cancers, the safety of CAR-macrophages remains promising. Pembrolizumab is known to be safe in similar situations, so its use with CAR-macrophages provides a reassuring safety background.

Early results also suggest that administering CAR-macrophages directly into the abdomen is safe and manageable for patients. The treatment did not cause unexpected or severe side effects, supporting further research.

These findings are encouraging, especially since this is a Phase 1 trial where safety is the main focus. The positive safety profile of CAR-macrophages is a good sign for those considering joining this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR-macrophages combined with pembrolizumab for HER2-positive cancer because this approach is novel and potentially transformative. Unlike traditional treatments that often involve chemotherapy or targeted therapies like trastuzumab, CAR-macrophages use genetically engineered immune cells designed to seek out and destroy cancer cells more precisely. This new mechanism of action could offer a more targeted attack on tumors, reducing collateral damage to healthy cells. Additionally, combining CAR-macrophages with pembrolizumab, an immune checkpoint inhibitor, might amplify the immune response, offering a powerful one-two punch against cancer. This innovative approach has the potential to significantly improve outcomes for patients with HER2-positive cancer.

What evidence suggests that this trial's treatments could be effective for HER2 positive cancer?

This trial will evaluate the effectiveness of CAR-macrophages and their combination with pembrolizumab for treating HER2-positive cancer. Studies have shown that CAR-macrophages, specially designed immune cells, hold promise in treating HER2-positive cancer by attacking cancer cells. In earlier research, these cells shrank tumors and extended the lives of lab animals. Initial results in patients showed that the disease remained stable in 28.6% of cases, suggesting some ability to combat the cancer.

In this trial, one group of participants will receive CAR-macrophages alone, while another group will receive CAR-macrophages combined with pembrolizumab, a current cancer medication. This combination might enhance the body's immune response against tumors, possibly leading to better outcomes. Both treatments are still in the early stages of testing, but initial data suggests they could be effective. ^{1 2 3 4 5}

Who Is on the Research Team?

Jeanett Wetzel

Principal Investigator

Carisma Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with HER2-positive solid tumors that have no curative treatments left. They must have tried all standard therapies, and if they have breast or gastric cancers, also failed HER2-targeted drugs. Participants need to be relatively healthy (ECOG 0-1) and able to undergo biopsies. Those with heart issues, active autoimmune diseases, organ transplants, certain infections or severe allergies to the study drug can't join.

Inclusion Criteria

My cancer is HER2-positive, has returned or spread, and cannot be cured with available treatments.

I am fully active or can carry out light work.

My HER2-positive cancer has not responded to standard treatments.

Exclusion Criteria

I have received an organ or tissue transplant from another person.

I have an immune system disorder or I'm on long-term steroids or other drugs that weaken my immune system.

You have a severe allergic reaction to pembrolizumab or any of its ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CT-0508, with or without pembrolizumab, through IV or IP administration with dose escalation over several days

1 week

Multiple visits for dose escalation on Days 1, 3, and 5

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and objective response rate assessments

24 months

Safety Monitoring

Assess the safety and tolerability of CT-0508, including frequency and severity of adverse events

14 months

What Are the Treatments Tested in This Trial?

Interventions

• CAR-macrophages

Trial Overview The trial is testing a new therapy called CT-0508 in combination with an existing cancer drug named Pembrolizumab on patients with various types of advanced cancer that overexpresses HER2 protein. It's a phase 1 study which means it's the first time this treatment is being used in humans to check its safety.

How Is the Trial Designed?

Group I: Intraperitoneal Administration Experimental Treatment 1 Intervention

All cohorts will receive the full dose manufactured per patient. Cohorts 1-3 will undergo intrasubject dose escalations of IP administration as follows: Cohort 1 up to 500 million total cells on Day 1, up to 1 billion total cells on Day 3 and up to 1.5 billion total cells on Day 5. Cohort 2 up to 1.5 billion total cells on Day 1, up to 2 billion total cells on Day 3 and any remaining cells on Day 5. Cohort 3 up to 2.5 billion total cells on Day 1 and up to 2.5 billion total cells on Day 3. Cohort 4 will 1 dose on Day 1 of up to 5 billion total cells.

Group II: Group 1 and Group 2 Experimental Treatment 1 Intervention

Both groups will receive the full dose manufactured per patient. Group 1 will undergo intra subject dose escalation of IV administrations of up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5. Group 2 will receive the full dose IV on Day 1 of up to 5 billion cells total.

Group III: CT-0508 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

All regimen levels will receive the full dose manufactured per patient up to 5 billion total cells. Regimen Levels 1 and 2 will undergo intrasubject dose escalations of IV administration as follows: Regimen Level 1: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 8. Regimen Level 2: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 1. Regimen Level 3 will receive the full dose IV on Day 1 of up to 5 billion total cells plus pembrolizumab 200 mg q3w starting on Day 1.

Group IV: 89[Zr]radiolabeled CT-0508 Experimental Treatment 1 Intervention

89\[Zr\] radiolabeled group will receive a full dose IV on Day 1 of up to 500 million total cells of 89\[Zr\] radiolabeled CT-0508 and non-radiolabeled CT-0508 of up to 4.5 billion total cells (Univ of Penn Abramson Cancer Center only).

Who Is Running the Clinical Trial?

Carisma Therapeutics Inc

Lead Sponsor

Trials

2

Recruited

50+

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO2-04-08/744336/Abstract-PO2-04-08-Translational-insights-from-a

Abstract PO2-04-08: Translational insights from a phase 1, first ... Conclusions: CT-0508 was feasible to manufacture and had acceptable safety and tolerability. Early correlative data demonstrate trafficking, TME ...

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04660929

Study Details | NCT04660929 | CAR-macrophages for the ... Estimate the objective response rate (ORR), according to RECIST v1.1, of at least 1 dose of CT-0508 among subjects with HER2 overexpressing solid tumors.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39920391/

CAR-macrophage therapy for HER2-overexpressing ... We report results from a non-prespecified interim analysis of a first-in-human, phase 1 clinical trial of CT-0508, an anti-human epidermal ...

5. onclive.com onclive.com/view/car-m-therapy-ct-0508-shows-promise-in-her2-overexpressing-recurrent-metastatic-solid-tumors

CAR-M Therapy CT-0508 Shows Promise in HER2 ... Among patients who received CT-0508 (n = 14), the best overall response per RECIST v1.1 criteria was stable disease, which occurred in 28.6% of ...