Engineered T Cells + Pembrolizumab for Pleural Cancer

Recruiting at 6 trial locations

Overseen By Roisin O'Cearbhaill, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticonvulsants, Corticosteroids, Immunosuppressants, others

Disqualifiers: CNS metastases, Seizure disorder, Autoimmune diseases, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

113 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this Phase I study is to test the safety of different doses of specially prepared immune cells (called "T cells") collected from blood. The Investigators want to find a safe dose of these modified T cells for patients who have malignant pleural disease. They want to find out what effects these T cells have on the patient and the cancer (MPD). Phase 2 part of the study, the investigators will test the dose in combination with another drug, pembrolizumab, to see what effects the study treatment has on malignant pleural mesothelioma.

Research Team

Roisin O'Cearbhaill, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with malignant pleural diseases like lung cancer or mesothelioma, who've had at least one prior treatment and show disease progression. They must have a functional pleural catheter, meet specific lab criteria (like certain blood cell counts), not be pregnant or breastfeeding, agree to use contraception, and can't have autoimmune diseases or need daily steroids.

Inclusion Criteria

I finished my chemotherapy at least a week ago.

I am 18 years or older with a myeloproliferative disorder.

It has been over 28 days since my last major chest or belly surgery.

Exclusion Criteria

I have not received any live vaccines in the last 8 weeks.

My breast cancer has spread to the lining of my lungs and needs immediate treatment.

I have not had serious heart issues or uncontrolled infections in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

T Cell Preparation

Leukapheresis product is obtained and T cells are isolated, transduced, and expanded

3-6 weeks

Treatment

Participants receive CAR T cell infusion, with or without cyclophosphamide, followed by pembrolizumab administration

12 weeks

Weekly visits for the first four weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cyclophosphamide
• iCasp9M28z T cell infusions
• Pembrolizumab

Trial Overview The study tests different doses of genetically engineered T cells targeting the antigen Mesothelin in patients with malignant pleural disease. It aims to find a safe dose and observe its effects on the patient's body and cancer. Phase II will combine these T cells with pembrolizumab to further assess effectiveness.

Participant Groups

Group I: modified T cells with cyclophosphamide Experimental Treatment 2 Interventions

Patients will receive cyclophosphamide intravenously (at 1.5 g/m\^2) , 2 - 7 (Day (-7) -(-2) days before T cell infusion. On Day 1 , patients will be admitted to the MSKCC Inpatient Service (if not already inpatients) for intravenous hydration, clinical monitoring, and blood work for immune monitoring. Standard MSKCC antiemetic therapy will be administered prior to chemotherapy to prevent nausea/vomiting. Administration of corticosteroids will be avoided as steroids may impede the efficacy of CAR T cells.

Group II: modified T cells alone (without chemotherapy) Experimental Treatment 1 Intervention

Following enrollment, leukapheresis product will be obtained in the blood donor facility at MSKCC and cryopreserved in the Cell Therapy and Cell Engineering Facility (CTCEF). Before protocol treatment, the leukapheresis product will be thawed, and T cell isolation, transduction, and expansion of iCasp928z T cells will be performed in the MSKCC CTCEF Facility. It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment.

Group III: CAR T cell and pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 4 weeks (+3/-1 week window) after completing CAR T cell administration. Patients will receive 3 doses of pembrolizumab given on a recurring schedule followed by reassessment. Those responding or deriving clinical benefit, without unacceptable toxicity, will continue pembrolizumab. Patients will be followed weekly for the first four weeks. Patients in cohorts 9 and in Phase II will receive pembrolizumab 4 weeks(+3/- 1 week window) following CAR T cell administration.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bellicum Pharmaceuticals

Industry Sponsor

Trials

28

Recruited

1,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+