Engineered T Cells + Pembrolizumab for Pleural Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine safe doses for a new treatment using specially prepared immune cells called T cells to address malignant pleural disease, a cancer affecting the lung lining. Initially, the study will examine the effects of these modified T cells alone, followed by their combination with pembrolizumab, an immunotherapy drug, to assess their joint effectiveness against cancer. Individuals with malignant pleural disease, such as pleural mesothelioma or certain lung and breast cancers that have spread to the pleura and progressed after prior treatment, may qualify for participation. The trial focuses on testing the safety and impact of these treatments on cancer. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications before joining the trial. Chemotherapy or targeted therapy must be stopped at least 14 days before receiving T cells, and prior immunotherapy must be stopped more than a month before. However, you can continue hormonal therapy for breast cancer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the safety of iCasp9M28z T cell infusions has been studied before. In one case, a patient experienced a serious allergic reaction during a similar CAR T cell treatment. However, other studies found that patients did not experience side effects outside the intended areas, indicating that while some risks exist, side effects are generally manageable.

When iCasp9M28z T cells are combined with cyclophosphamide, studies found no side effects in unintended areas, which is a positive indicator for safety. Cyclophosphamide is often used to enhance T cell efficacy.

Less specific safety information is available for the combination of iCasp9M28z T cells with pembrolizumab. However, pembrolizumab is an approved drug for other cancers, providing some reassurance about its safety.

Overall, while some risks may exist, these treatments have generally been well-tolerated in earlier studies. This trial aims to further explore these aspects to ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer novel approaches to tackling pleural cancer. Unlike traditional treatments that often rely on chemotherapy, these investigational treatments focus on engineered T cells, with some arms using them alone or in combination with cyclophosphamide or pembrolizumab. The iCasp9M28z T cells are modified to specifically target cancer cells, potentially enhancing the immune system's ability to fight the disease. Cyclophosphamide is used to prepare the body for T cell infusion by suppressing the immune system, making it more receptive to the engineered cells. Pembrolizumab works by blocking a pathway that tumors use to evade immune detection, thus boosting the immune response when used after CAR T cell administration. This combination of targeted immune therapies could offer more effective and personalized treatment options for patients with pleural cancer.

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

Research has shown that iCasp9M28z T cell infusions could be promising for treating malignant pleural mesothelioma, a type of cancer. These specially designed T cells target cancer cells, potentially leading to better treatment outcomes. In this trial, some participants will receive these T cells alone, while others will receive them with cyclophosphamide. Studies suggest cyclophosphamide can help the T cells enter tumors more effectively. Another group will receive the T cells combined with pembrolizumab, a drug that helps the immune system fight cancer, which has achieved a 72% response rate in similar cases. This combination may enhance the body's ability to combat pleural cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Roisin O'Cearbhaill, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02414269

Study Details | NCT02414269 | Malignant Pleural Disease ... It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment. Intervention/Treatment, Genetic : iCasp9M28z T cell infusions.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7080957/

Emerging Treatments for Malignant Pleural Mesothelioma Pre-clinical evidences showed that dendritic cell therapy leads to better outcome when dendritic cells are injected in murine models with lower ...

3. lungcancerjournal.info lungcancerjournal.info/cms/10.1016/j.lungcan.2022.01.003/attachment/2cfca633-78c6-4dc6-b56a-33a5ee029506/mmc2.pdf

memorial sloan-kettering cancer center irb protocol irb#: 15-007 Pleural biopsies will be performed to assess tumor T cell infiltration—specifically iCasp9M28z T cell infiltration—in tumor and surrounding tissues. Flow ...

4. app.emergingmed.com app.emergingmed.com/su2c/trial/96524

Stand Up to Cancer Clinical Trial Navigation Service It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment. Intervention / treatment: Genetic: iCasp9M28z T cell infusions.

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33433

Malignant mesothelioma: Advances in immune checkpoint ... In this review, the authors describe recent advances in therapeutic strategies for the treatment of patients with advanced, unresectable mesothelioma.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7480947/

Current Advances in CAR T Cell Therapy for Malignant ... Interestingly, an immediate serious anaphylactic reaction was noted in one patient during a delayed mesothelin CAR T cell infusion that was attributed to the ...

7. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-021-00264-1/tables/1

Anti-Mesothelin CAR T cell therapy for malignant mesothelioma Positive results (Primary endpoint: safety). Low persistence and low tumor infiltration were observed. Best OR: 6/15 patients with SD (Ref. 34). NCT03054298.