NCT02399371 · REGISTRY CONDITION SEARCH

Pembrolizumab in Treating Patients With Malignant Mesothelioma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2026-05-08

This phase II trial studies how well pembrolizumab works in treating patients with malignant mesothelioma, a cancer of the linings around the lungs (pleura) or abdomen (peritoneum). Monoclonal antibodies, such as pembrolizumab, work by blocking a protein called programmed cell death 1 (PD-1) which may stimulate an immune response and kill tumor cells.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Ability of PD-L1 to Predict Response

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Disease Control Rate (CR + PR + SD)

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outcome · POSTED

CD8 TILs Will be Assessed by Percentage of Tumor Showing Infiltration

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outcome · POSTED

Composite Measure of Other Immune Escape Mechanisms Including MDSCs and Other Checkpoints

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outcome · POSTED

PD-L1 Expression by Mass Spectrometry

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outcome · POSTED

Mass Spectrometry-based Flow Cytometric Analysis

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outcome · POSTED

Analysis of T-cell Receptor Repertoire From TILs

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outcome · POSTED

Duration of Response

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outcome · POSTED

Incidence of Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histologically or cytologically confirmed pleural or peritoneal malignant mesothelioma, epithelial, sarcomatoid, or biphasic subtypes * Disease progression on or after pemetrexed and cis- or carboplatin * ONLY FOR PART B - PD-L1 selection should a PD-L1 expression threshold have been defined in Part A and potentially additional mesothelioma trial data; there will be no PD-L1/biomarker selection for Part A * No more than 2 prior lines of cytotoxic therapy, which should have included pemetrexed and a platinum * Enrollment of treatment naïve patients who refuse standard chemotherapy or are intolerant may be permissible if reviewed and deemed clinically appropriate by the principal investigator (PI) * Be willing and able to provide written informed consent for the trial * Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for peritoneal mesothelioma, and modified RECIST for pleural mesothelioma * Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion; while 20 unstained slides or a tumor block are preferred, at least 14 unstained slides are requested for analysis; PI approval for a lower number of slides is acceptable * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Absolute neutrophil count (ANC) \>= 1,500/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 9 g/dL * Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 50 mL/min for subject with creatinine levels \> 1.5 X institutional ULN; creatinine clearance should be calculated per institutional standard * Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases * International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants * Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: * Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks (4 weeks for monoclonal antibodies) of the first dose of treatment * Side effects from prior treatment have not resolved to =\< grade 1 (or baseline due to previously administered agent/pre-existing conditions) * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment * Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or other indolent cancers which either have undergone curative-intent therapy or inactive (i.e. not expected to limit life expectancy or interfere with therapy) * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment * Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study * Has evidence of interstitial lung disease or active, non-infectious pneumonitis * Has an active infection requiring systemic therapy * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) * Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) * Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected) * Has received a live vaccine within 30 days prior to the first dose of trial treatment
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible for up to 1 year of additional pembrolizumab therapy if they progress after stopping pembrolizumab.
intervention Names
Biological: Pembrolizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacogenomic Study
label
Treatment (pembrolizumab)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (pembrolizumab)
description
Given IV
name
Pembrolizumab
other Names
Keytruda
Lambrolizumab
MK-3475
SCH 900475
type
BIOLOGICAL
arm Group Labels
Treatment (pembrolizumab)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Treatment (pembrolizumab)
description
Correlative studies
name
Pharmacogenomic Study
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 65
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
CD8 levels will be correlated with PD-L1 expression using Pearson or Spearman rank correlation coefficients.
measure
CD8 TILs Will be Assessed by Percentage of Tumor Showing Infiltration
time Frame
Baseline
description
Other immune escape mechanisms including MDSCs and other checkpoints will be assessed by immunohistochemistry (0 - 3+) or flow cytometry counting the number and percentage of positive cells. Levels will be correlated with PD-L1 expression and other biomarkers.
measure
Composite Measure of Other Immune Escape Mechanisms Including MDSCs and Other Checkpoints
time Frame
Up to 5 years
description
PD-L1 expression by mass spectrometry and correlation with PD-L1 expression by IHC as well as tumor response, and the T-cell inflamed phenotype will be performed. Multivariate logistic regression will be performed to determine whether these biomarkers or combinations of biomarkers are predictive of response. Exact logistic regression models will be fit given the small number of responders expected (4 from part A and 7-8 from part B).
measure
PD-L1 Expression by Mass Spectrometry
time Frame
Baseline
description
Mass spectrometry-based flow cytometric analysis (CyTOF) will be descriptive based on number and percentage of certain cell populations.
measure
Mass Spectrometry-based Flow Cytometric Analysis
time Frame
Up to 5 years
description
Analysis of T-cell receptor repertoire from TILs will be descriptive looking for presence or absence of oligoclonal T-cell population.
measure
Analysis of T-cell Receptor Repertoire From TILs
time Frame
Up to 5 years
description
Time from detection of response to disease progression or death, estimated by Kaplan-Meier with 95% confidence interval using the Brookmeyer-Crowley method.
measure
Duration of Response
time Frame
Up to 5 years
description
Number of patients having any adverse event.
measure
Incidence of Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
time Frame
Up to 30 days after completion of study treatment, maximum of 5 years.

primary Outcomes

description
The Youden Index will be used to determine the optimal threshold for PD-L1 expression in correlation with tumor response. Youden Index ranges from 0-1 with higher scores meaning greater accuracy/sensitivity/specificity calculated from an ROC AUC (sensitivity + specificity - 1 = Youden Index).
measure
Ability of PD-L1 to Predict Response
time Frame
Up to 1 year

secondary Outcomes

description
Kaplan-Meier curves will be generated for OS. Median OS will be estimated along with 95% confidence intervals using the method of Brookmeyer and Crowley.
measure
Overall Survival (OS)
time Frame
Up to 5 years
description
Kaplan-Meier curves will be generated for PFS. Median PFS will be estimated along with 95% confidence intervals using the method of Brookmeyer and Crowley.
measure
Progression Free Survival (PFS)
time Frame
Time from enrollment until disease progression or death from any cause, assessed up to 5 years
description
The disease control rate (CR+PR+SD) and 90% confidence interval will also be determined. Per Response Evaluation Criteria In Solid Tumors Criteria modified for immunotherapy (iRECIST) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), \>=120% increase in the sum of the longest diameter of target lesions; Stable disease (SD), not meeting criteria for either CR, PR, or PD. Per iRECIST, if criteria indicate PD, tumor assessment should be repeated 4 weeks later in order to confirm PD.
measure
Disease Control Rate (CR + PR + SD)
time Frame
Up to 1 year

Full study description

brief Summary: This phase II trial studies how well pembrolizumab works in treating patients with malignant mesothelioma, a cancer of the linings around the lungs (pleura) or abdomen (peritoneum). Monoclonal antibodies, such as pembrolizumab, work by blocking a protein called programmed cell death 1 (PD-1) which may stimulate an immune response and kill tumor cells.
detailed Description: PRIMARY OBJECTIVES: I. To determine the objective response rate of patients with malignant mesothelioma treated with pembrolizumab in A) an unselected patient population, as well as B) in a programmed cell death ligand 1 (PD-L1) positive population (should the trial proceed to Part B, and PD-L1 expression correlate with improved efficacy). II. To determine the optimal threshold for PD-L1 expression using the 22C3 antibody based immunohistochemistry (IHC) assay in correlation to tumor response. SECONDARY OBJECTIVES: I. To determine the progression-free survival of patients with malignant mesothelioma in A) an unselected patient population and B) a PD-L1 positive population when treated with pembrolizumab. II. To determine the overall survival of patients with malignant mesothelioma in A) an unselected patient population and B) a PD-L1 positive population when treated with pembrolizumab. III. To determine the disease control rate (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]) of patients with malignant mesothelioma who are treated with pembrolizumab in A) an unselected patient population and B) a PD-L1 positive population. IV. To determine toxicity in patients with malignant mesothelioma who are treated with pembrolizumab. V. To determine percentage of patients with mesothelioma who have PD-L1 tumor expression, and the distribution of PD-L1 expression (percent positivity of tumor cells/stroma staining). TERTIARY OBJECTIVES: I. To characterize the T-cell inflamed phenotype in mesothelioma patients via presence of cluster of differentiation (CD)8 tumor infiltrating lymphocytes (TILs) and/or use of a gene expression signature (Nanostring). II. To evaluate other immune escape mechanisms including indoleamine-pyrrole 2,3-dioxygenase (IDO) expression, regulatory T cells (Tregs) (forkhead box P3 \[FOXP3\] expression), myeloid-derived suppressor cells (MDSCs) and other checkpoints by immunohistochemistry (or other methods e.g. flow cytometry). III. To determine PD-L1 expression by mass spectrometry and correlate with tumor response, PD-L1 expression by IHC, and the T-cell inflamed phenotype. IV. To determine the immune cell populations present in fresh tumor (when available), via tumor digests and mass spectrometry-based flow cytometric analysis (e.g. using CyTOF) in a multiplex fashion in patients with fresh tumor tissue. V. To characterize the T-cell receptor repertoire of TILs compared to circulating T-cells in mesothelioma patients with available fresh frozen tissue (spectrotyping, T-cell repertoire sequencing \[e.g. using the Adaptive platform\]). OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible for up to 1 year of additional pembrolizumab therapy if they progress after stopping pembrolizumab. After completion of study treatment, patients are followed up for 30 days (up to 90 days for serious adverse events), every 8 weeks until patient experiences confirmed disease progression or starts a new anti-cancer therapy, and then every 12 weeks for 3 years.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice