Fast TIL therapy for cancers that have spread to the pleura

Fast TILs to Treat Metastatic Cancer Patients With Pleural Disease: A Phase I Trial

This treatment will try a patient's own pleural T cells, grown quickly in the lab and given into the chest with local IL-2, for adults whose cancer has spread to the pleura or for pleural mesothelioma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 79 Years
• Sex: All
• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) (other)
• Drugs / interventions: radiation, prednisone, chemotherapy, immunotherapy
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT07192900 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1 trial collects pleural fluid, isolates pleural infiltrating T cells (PIT), and performs a short-term laboratory expansion to create an adoptive cellular therapy product. Participants receive outpatient lymphodepleting chemotherapy before the intrapleural infusion to create space for the transferred cells. The expanded PIT cells are delivered through a pleural catheter and accompanied by two days of intrapleural IL-2 to boost local activity while limiting systemic exposure. Ancillary studies will analyze drained pleural effusions before and after treatment to study why the therapy succeeds or fails.

Who should consider this trial

Good fit: Adults aged 18–79 with biopsy-proven malignant pleural effusion or pleural mesothelioma who have exhausted standard treatment options, can undergo lymphodepleting chemotherapy, and meet cardiac and reproductive-safety requirements are the intended candidates.

Not a fit: Patients without pleural disease, those who still have effective standard treatment options, or those medically unfit for lymphodepletion or with inadequate cardiac function are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this therapy could reduce tumor burden in the pleura and relieve fluid-related symptoms such as shortness of breath.

How similar studies have performed: Systemic TIL therapies have shown strong results in melanoma and some solid tumors, but using short-term expanded pleural T cells delivered intrapleurally with IL-2 is a novel, first-in-human approach and remains largely untested.

Eligibility criteria

Inclusion Criteria:

1. Patients with symptomatic, biopsy-proven malignant to the pleura, or mesothelioma with pleural effusions. Patients must have received and be refractory to available standard of care (SOC) therapy specific to their cancer type and must have exhausted or failed available standard of care with clinical benefit.
2. Patients will be ≥ 18 and \< 80 years of age.
3. Female patients of childbearing potential must have a negative urine or serum pregnancy test and if sexually active must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), an injectable contraceptive (such as Depo-Provera), or an oral contraceptive. Active contraception should continue for at least 6 months after ACT administration. Male participants must be willing to practice birth control from the time of enrollment on this study and for 6 months after receiving the preparative regimen.
4. Cardiac ejection fraction ≥ 0.45 by Multiple-Gated Acquisition (MUGA) or echocardiography.
5. No requirement for supplemental oxygen and no dyspnea immediately after effusion drainage.
6. Karnofsky performance score ≥ 70.
7. Patients must have an expected survival \> 12 weeks.
8. Patients must be able to comprehend the risks and methods used in this clinical trial and independently consent to participate.
9. Patients must consent to collection of demographic and clinical data.

Exclusion Criteria:

1. Patients with breast, kidney, lung, pancreatic, prostate, ovarian, rare cancers, and melanoma.
2. Infection with Human Immunodeficiency Virus (HIV) and active viral replication. Patients with an undetectable viral load on Anti-retroviral Therapy (ART) can be considered for participation on this protocol.
3. Infection with hepatitis B and active viral replication.
4. Infection with hepatitis C and active viral replication.
5. Patients currently being treated for bacterial, fungal or viral infection.
6. Documented myocardial infarction within 6 months of study participation and/or symptomatic coronary artery or valvular disease or uncontrolled arrhythmia.
7. Investigational drug use within 30 days before effusion collection.
8. Cytotoxic anti-cancer or radiation therapy administration within 2 weeks of effusion collection. The exclusion does not apply to patients receiving monoclonal antibody therapy targeting immune checkpoint molecules.
9. Corticosteroid therapy \> 10 milligrams (mg) of prednisone (biological equivalent) daily within 2 weeks before effusion collection.
10. Immunosuppressive therapy that cannot be stopped for 4 weeks prior to effusion collection as deemed by the prescribing physician.
11. Laboratory abnormalities that indicate clinically significant hematological, hepatobiliary, or renal disease:

    AST/SGOT \> 2.0 times the upper limit of normal ALT/SGPT \> 2.0 times the upper limit of normal Total bilirubin \> 2.0 times the upper limit of normal, unless patient has Gilbert Syndrome (\>3.0 times the upper limit of normal) Hemoglobin \< 8 gm/dL or dependent upon transfusion to maintain ≥ 8 gm/dL White blood cell count \< 2,000/mm3 Platelet count \< 100,000/mm3 or dependent upon transfusion to maintain ≥ 100,000 mm3 Creatinine \> 2.0 times the upper limit of normal or calculated creatinine clearance ≤ 40 mL/min.
12. Pregnant or lactating females.
13. Prior solid organ transplantation
14. Patients who, in the opinion of the Investigator, will be non-compliant with study schedules or procedures.
15. Patients who belong to a vulnerable population such as the homeless, the developmentally disabled and prisoners or have any condition that impairs their ability to provide informed consent or comply with study schedules or procedures.
16. Patients with documented anaphylaxis as a result of penicillin allergy.

Where this trial is running

Pittsburgh, Pennsylvania

• AHN West Penn Hospital — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: David Bartlett, MD — Allegheny Health Network
• Study coordinator: David Bartlett, MD

Conditions: Malignant Pleural Effusion, Malignant Mesothelioma, Pleural Effusion, Malignant, Metastasis to Pleura, metastasis to pleura, pleural infiltrating T cells, CliniMACS Prodigy, malignant mesothelioma