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CAR T-cell Therapy

Engineered T Cells + Pembrolizumab for Pleural Cancer

Phase 1 & 2

Waitlist Available

Led By Marjorie Zauderer, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Chemotherapy must have been completed at least 7 days prior to leukapheresis

Any major thoracic or abdominal operation must have occurred at least 28 days before study enrollment

Must not have

Breast cancer metastatic to the pleura that extends outside of the pleura requiring immediate therapy

Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of different doses of modified T cells for patients with malignant pleural disease. They will also test the combination of the T cells with another drug, pembrolizumab, to see what effect it has on the cancer.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include immune reactions due to modified T cells attacking healthy tissue, infusion-related reactions from the T cell therapy or pembrolizumab, fatigue from cyclophosphamide chemotherapy, as well as increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I finished my chemotherapy at least a week ago.

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

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I am able to care for myself but may not be able to do active work.

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My cancer in the lining of the lungs has been confirmed.

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All side effects from my past cancer treatments have mostly gone away.

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I finished palliative radiotherapy at least 2 days before starting cyclophosphamide.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have or had lung inflammation treated with steroids.

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I need daily corticosteroids or other drugs that affect my immune system.

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I have an autoimmune or antibody-mediated disease.

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I am currently being treated for another active cancer.

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

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I have brain metastases that haven't been treated.

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I have a history of seizures.

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My heart's pumping ability is below normal.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Composite measure of severity and number of adverse events (AEs); changes in (clinical laboratory test findings (hematologic and chemistry); and physical examination. (Phase I)

clinical benefit rate (phase II)

Secondary study objectives

Changes in serum levels of the biomarker soluble mesothelin related peptide (SMRP) (Phase I)

Side effects data

From 2024 Phase 3 trial • 453 Patients • NCT03062358

36%

Aspartate aminotransferase increased

30%

Alanine aminotransferase increased

28%

Blood bilirubin increased

21%

Platelet count decreased

18%

Gamma-glutamyltransferase increased

17%

White blood cell count decreased

17%

Pyrexia

16%

Diarrhoea

15%

Anaemia

15%

Decreased appetite

15%

Rash

14%

Blood alkaline phosphatase increased

14%

Neutrophil count decreased

12%

Hypoalbuminaemia

12%

Pruritus

11%

Cough

11%

Upper respiratory tract infection

10%

Proteinuria

10%

Hypothyroidism

10%

Lymphocyte count decreased

Constipation

Arthralgia

Weight decreased

Abdominal pain

Nausea

Bilirubin conjugated increased

Insomnia

Asthenia

Fatigue

Hyperglycaemia

Hypokalaemia

Hyponatraemia

Hypoproteinaemia

Back pain

Hypertension

Vomiting

Abdominal distension

Blood lactate dehydrogenase increased

Hyperthyroidism

Ascites

Abdominal pain upper

Hepatitis B DNA increased

Malaise

Blood glucose increased

Blood creatinine increased

Upper gastrointestinal haemorrhage

Pneumonia

Dyspepsia

Gastrointestinal haemorrhage

Autoimmune hepatitis

Hepatic failure

Hepatitis E

Influenza

Sepsis

Tumour haemorrhage

Hepatic encephalopathy

Pneumonitis

Dysphonia

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab (First Course) + BSC

Placebo + BSC

Pembrolizumab Second Course

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: modified T cells with cyclophosphamideExperimental Treatment2 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 Treatment1 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 pembrolizumabExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

cyclophosphamide

1994

Completed Phase 3

~8140

pembrolizumab

2017

Completed Phase 3

~5890