Fast TILs + Interleukin-2 for Mesothelioma

((RIOT 4A) Trial)

Overseen By AHN Clinical Trial Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: David Bartlett, MD

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Breast cancer, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called Fast TILs, which uses a person’s own immune cells to combat pleural mesothelioma, a cancer affecting the lung lining. The treatment involves collecting T-cells from the patient’s pleural fluid, expanding them in a lab, and then delivering them back to the patient with Interleukin-2, a protein that boosts the immune system, to help fight the tumor. The trial aims to determine the safety and effectiveness of this approach. It is designed for individuals with pleural mesothelioma who have not responded to standard treatments and experience symptoms like pleural effusions, or fluid build-up around the lungs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that certain therapies, like immunosuppressive therapy, must be stopped 4 weeks before effusion collection. It's best to discuss your specific medications with the trial team.

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

Research has shown that tumor-infiltrating lymphocyte (TIL) therapy, such as the Fast TILs being tested, has produced promising results in treating certain cancers. In other studies, about 22% of patients experienced complete tumor disappearance, with tumors remaining gone for over three years.

However, the Fast TILs treatment combined with Interleukin-2 (IL-2) is new and has not been tested in humans before. Its safety is not yet fully understood. Although similar treatments have been used safely, there remains a risk of serious side effects.

Researchers will closely monitor participants for any negative reactions, which is common in early studies like this one. Those considering joining the trial should discuss the potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Fast TILs for mesothelioma because it offers a personalized approach that targets the cancer with the patient's own immune cells. Unlike conventional treatments like chemotherapy and radiation, which can affect healthy cells, Fast TILs utilize T-cells extracted from the patient's tumor, potentially leading to a more precise attack on cancer cells. Additionally, this treatment is delivered directly into the pleural cavity through a catheter, allowing for concentrated, localized therapy. Combined with low-dose Interleukin-2, which helps boost the immune response, Fast TILs could offer a more targeted and effective treatment option.

What evidence suggests that Fast TILs might be an effective treatment for mesothelioma?

Research has shown that tumor-infiltrating lymphocytes (TILs), such as those in Fast TILs, can improve cancer treatment outcomes. Studies have found that a higher presence of these TILs correlates with better survival rates in various cancers, including mesothelioma. One study demonstrated that TIL therapy controlled the disease in 80% of patients, preventing cancer progression. Additionally, 36% of patients experienced a significant reduction in tumor size. In this trial, participants will receive a locally manufactured adoptive cellular therapeutic (ACT) product derived from autologous pleural infiltrating T-cells, known as Fast TILs. The addition of Interleukin-2 (IL-2) will activate these cells, enhancing their ability to combat the tumor. ^{6 7 8 9 10}

Who Is on the Research Team?

David Bartlett, MD

Principal Investigator

Allegheny Health Network

Are You a Good Fit for This Trial?

This trial is for patients with cancer that has spread to the lining of their lungs (pleura) or have pleural mesothelioma. They must be able to undergo a procedure to collect pleural fluid and receive outpatient chemotherapy before getting the new treatment through a catheter.

Inclusion Criteria

I am between 18 and 79 years old.

Expected survival > 12 weeks

My cancer in the lining of the lungs is not responding to standard treatments.

Exclusion Criteria

I have HIV with active viral replication.

I have not had a recent heart attack or uncontrolled heart problems.

I cannot stop my immunosuppressive therapy for 4 weeks before fluid collection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants undergo outpatient lymphodepleting chemotherapy before receiving the ACT product

1 week

Treatment

Participants receive the ACT product through a pleural catheter, followed by IL-2 administration for two days

3 weeks

Potential hospital stay of up to six days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits over five years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Fast TILs

Trial Overview The study tests Fast TIL, an immunotherapy using patient's own immune cells (PIT), combined with Interleukin-2. The goal is to see if this can fight cancer in the pleura more effectively than current treatments and improve symptoms.

How Is the Trial Designed?

Group I: locally manufactured adoptive cellular therapeutic (ACT) product Experimental Treatment 2 Interventions

Single dose, intrapleural delivery (via indwelling pleural catheter) of adoptive cellular therapy (ACT) product derived from autologous pleural infiltrating T-cells. Low dose Interleukin-2 (IL-2) will also be administered intrapleural at the dose of 20 milliliters (mL) at 1 x 10⁵ International Units (IU)/mL starting approximately 2 hours after ACT infusion and every 8 to 16 hours thereafter, as tolerated, for up to 4 doses (total 8 x 10⁶ IU).

Who Is Running the Clinical Trial?

David Bartlett, MD

Lead Sponsor

Miltenyi Biotec, Inc.

Industry Sponsor

Trials

11

Recruited

280+

UPMC Hillman Cancer Center

Collaborator

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11030611/

CD8+ tumor-infiltrating lymphocytes predict favorable ... CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection ... rapid fatal outcome in patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1556086423014776

P2.18-02 Successful Generation of Tumor-Infiltrating ... These feasibility data suggest that viable TIL can be successfully expanded from mesothelioma tumor tissue. ... Tumor-infiltrating lymphocytes, Mesothelioma, ...

3. nature.com nature.com/articles/s41698-025-00866-0

Prediction and analysis of tumor infiltrating lymphocytes ... Elevated proportion of TILs has been associated with improved survival outcomes in various cancers, but the prognostic significance of this ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e20064

Prognostic value of tumor infiltrating lymphocytes in ... The purpose of this study was to determine if tumor infiltrating lymphocytes (TIL) are correlated with survival in epithelioid MM. Methods: ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274268/

Tumor infiltration therapy: from FDA approval to next ... Mean amounts of TILs received by patients was 2.73 × 10^10, with 80% disease control rate (DCR), 36% objective response rate (ORR), 3% complete ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11743541/

The global trends and distribution in tumor-infiltrating ... This study utilizes bibliometric methodologies to identify emerging research hotspots and to map the distribution of tumor-infiltrating lymphocyte research.

7. jto.org jto.org/article/S1556-0864(23)01477-6/pdf

P2.18-02 Successful Generation of Tumor-Infiltrating ... The real-world safety profile of lurbinectedin in this analysis was generally consistent with those reported in the basket trial, with no new safety signals.

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.tps7586

Phase I/II study of tumor-infiltrating lymphocyte (TIL) ... Background: MPM is a disease with poor outcomes, and only modest benefits from existing systemic therapies. Preclinical studies have shown ...

9. link.springer.com link.springer.com/article/10.1007/s10238-025-01574-6

Tumor infiltration therapy: from FDA approval to next- ... The mean number of TILs administered was 2.8 × 1010; the overall response rate was 44% with one complete response, nine partial responses, and ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9651159/

Tumor-infiltrating lymphocytes for treatment of solid tumors Twenty of the 93 patients (22%) had complete tumor regression lasting beyond three years, with 100% and 93% of 3- and 5-year survival rates, respectively. The ...