Cell Therapy for Mesothelioma

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

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex. This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.

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.

What makes the treatment Gavo-cel (TC-210) unique for mesothelioma?

Gavo-cel (TC-210) is unique because it uses a T cell receptor fusion construct to target mesothelin, a protein often found on mesothelioma cells, and activates the body's immune response to attack the cancer. This approach is different from traditional treatments as it specifically harnesses the immune system to fight the tumor. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Gavo-cel (TC-210) for mesothelioma?

Research shows that CAR T-cell therapies targeting mesothelin, like Gavo-cel, have demonstrated safety and antitumor effects in patients with malignant pleural mesothelioma, with some patients experiencing stable disease and extended survival. Additionally, combining CAR T-cell therapy with pembrolizumab, an immune checkpoint inhibitor, has shown promising results in enhancing the treatment's effectiveness. ^{1 6 7 8 9}

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.

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

My heart pumps well and I don't have serious fluid around 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. United States pubmed.ncbi.nlm.nih.gov

New Immunotherapy Combinations Enter the Battlefield of Malignant Mesothelioma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

CAR T-cell immunotherapy of MET-expressing malignant mesothelioma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Gene therapy for malignant pleural mesothelioma: present and future. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. [2023]