Cell Therapy for Mesothelioma

Not currently recruiting at 11 trial locations

Overseen By Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: TCR2 Therapeutics

Disqualifiers: Diabetes, Hypertension, Bipolar, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called gavo-cel (TC-210) for individuals with certain cancers, such as mesothelioma, ovarian cancer, cholangiocarcinoma, or non-small cell lung cancer. The goal is to determine the optimal dose and evaluate the treatment's effectiveness, potentially in combination with other immuno-oncology drugs. Participants should have advanced cancer that expresses mesothelin, a protein found in some tumors, and must have tried at least one standard treatment. Those dealing with one of these cancer types and who have undergone previous treatments might be suitable for this trial. As a Phase 1/Phase 2 trial, this research aims to understand the treatment's effects in people and measure its effectiveness in an initial group, offering a chance to contribute to groundbreaking cancer therapy advancements.

Will I have to stop taking my current medications?

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 shows that gavo-cel, a new cell therapy, is generally safe. Studies found that a single dose given through an IV usually causes mild and manageable side effects, meaning most people can tolerate them without serious issues. The therapy also effectively controls the disease in many patients.

When combined with nivolumab, a type of immunotherapy, research indicates this combination is safe for patients with cancers that have a protein called mesothelin. This combination aims to strengthen the body's immune system to fight cancer.

Adding another immunotherapy, ipilimumab, to gavo-cel and nivolumab has also been tested. Previous studies suggest that using nivolumab and ipilimumab together is generally safe for patients with mesothelioma, implying that the three-drug combination might also be safe.

Since this study is in its early stages, the main goal is to ensure that gavo-cel, whether used alone or with other drugs, is safe for people. Early-phase trials focus on safety and provide initial insights into how people react to new treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about gavo-cel for mesothelioma because it represents a novel approach using cell therapy to target cancer cells. Unlike standard treatments like chemotherapy, which attack both healthy and cancerous cells, gavo-cel is designed to specifically target and destroy mesothelioma cells, potentially leading to fewer side effects. In some arms of the trial, gavo-cel is combined with immune checkpoint inhibitors like nivolumab and ipilimumab, which could enhance the body's immune response against the cancer. This combination approach aims to improve treatment efficacy and possibly lead to longer-lasting remission.

What evidence suggests that this trial's treatments could be effective for mesothelioma?

Studies have shown that gavo-cel, a new cell therapy, can help people with certain solid tumors, such as mesothelioma. Specifically, one study found that 77% of patients treated with gavo-cel experienced either stabilization or improvement of their disease. In this trial, participants may receive gavo-cel alone or in combination with nivolumab, with the success rate remaining at 77%. Another group will receive gavo-cel with both nivolumab and ipilimumab, which has maintained treatment effectiveness while managing side effects. These findings suggest that gavo-cel, alone or with other drugs, might help control mesothelioma by targeting specific markers on cancer cells. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical

Principal Investigator

TCR2 Therapeutics

Are You a Good Fit for This Trial?

Adults with certain advanced cancers (like mesothelioma, ovarian cancer, bile duct cancer, or lung cancer) that express a protein called Mesothelin can join this trial if they've already tried at least one standard treatment (except for bile duct cancer patients who may not have). They need to be fairly healthy and active, with good heart function and no serious fluid around the heart.

Inclusion Criteria

I've had at least one standard treatment for my advanced cancer before considering gavo-cel, except if I have Cholangiocarcinoma.

My heart pumps well and I don't have serious fluid around it.

I am healthy enough for a procedure to collect white blood cells and have good veins for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive fludarabine and cyclophosphamide for lymphodepletion

4 days

In-patient treatment

Treatment

Participants receive gavo-cel with or without nivolumab and ipilimumab

3 months

Nivolumab every 3 weeks, ipilimumab every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Gavo-cel (TC-210)

Trial Overview The study is testing gavo-cel (TC-210), a new type of T cell therapy designed to target Mesothelin on cancer cells. It's given alone or with immune-boosting drugs like Nivolumab and Ipilimumab. The goal is to find the best dose and see how well it works against these cancers.

How Is the Trial Designed?

Group I: Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab Experimental Treatment 5 Interventions

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel

Group II: Lymphodepletion followed by gavo-cel plus nivolumab Experimental Treatment 4 Interventions

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel

Group III: Lymphodepletion followed by gavo-cel Experimental Treatment 3 Interventions

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel

Who Is Running the Clinical Trial?

TCR2 Therapeutics

Lead Sponsor

Trials

3

Recruited

50+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

The study involved 15 patients with chemotherapy-refractory cancers, and the lentiviral-transduced CAR T cells targeting mesothelin (CART-meso) were generally well tolerated, with only one case of severe toxicity (sepsis) reported.

While CART-meso cells expanded in the blood and were detectable in tumor biopsies, the overall clinical response was limited, with the best outcome being stable disease in 11 out of 15 patients, indicating the need for further research into more effective CAR designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. Haas, AR., Tanyi, JL., O'Hara, MH., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8537

Phase 1 trial of gavocabtagene autoleucel (gavo-cel, TC- ... The 6-month OS rate was 70.2%. The ORR of pts with MPM or OvC receiving gavo-cel after LD was 21% and 29%, respectively. The median PFS and OS ...

2. nature.com nature.com/articles/s41591-023-02452-y

Mesothelin-targeting T cell receptor fusion construct ... Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors.

3. onclive.com onclive.com/view/gavo-cel-elicits-clinical-benefit-in-solid-tumors-including-ovarian-cancer-and-mesothelioma

Gavo-cel Elicits Clinical Benefit in Solid Tumors, Including ... Results showed that gavo-cel led to a disease control rate (DCR) of 77% in all evaluable patients with solid tumors (n = 30). Moreover, 93% of ...

4. stevenagecatalyst.com stevenagecatalyst.com/tcr-therapeutics-announces-positive-interim-results-ongoing-phase-12-trial-gavo-cel-treatment-refractory-mesothelin-expressing-solid-tumors/

TCR² Therapeutics Announces Positive Interim Results ... The interim gavo-cel data reported today showed continued clinical benefit and a manageable safety profile in a population of patients that previously achieved ...

5. aacrjournals.org aacrjournals.org/cancerres/article/81/13_Supplement/CT105/669855/Abstract-CT105-Preliminary-safety-and-efficacy-of

Preliminary safety and efficacy of gavocabtagene autoleucel ... The disease control rate was 100%. All patients experienced target lesion regression by CT: median 61% (range, 5-75%). Three (43%) patients (2 ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT03907852

Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With ... TCR2 to highlight additional safety, efficacy and translational data from all patients receiving therapy up to dose level 5 (second and third gavo-cel doses) ...