Trial Outcomes & Findings for Pembrolizumab in Treating Patients With Malignant Mesothelioma (NCT NCT02399371)
NCT ID: NCT02399371
Last Updated: 2026-05-08
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
65 participants
Primary outcome timeframe
Up to 1 year
Results posted on
2026-05-08
Participant Flow
Participant milestones
| Measure |
Treatment (Pembrolizumab)
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
65
|
|
Overall Study
COMPLETED
|
64
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (Pembrolizumab)
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Pembrolizumab in Treating Patients With Malignant Mesothelioma
Baseline characteristics by cohort
| Measure |
Treatment (Pembrolizumab)
n=64 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Age, Continuous
|
68 years
n=41 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=41 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=41 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=41 Participants
|
|
Race (NIH/OMB)
White
|
59 Participants
n=41 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
|
Region of Enrollment
United States
|
64 participants
n=41 Participants
|
PRIMARY outcome
Timeframe: Up to 1 yearPopulation: Two patients had missing PD-L1 expression data.
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).
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=62 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Ability of PD-L1 to Predict Response
|
0.377 Youden index
Interval 0.136 to 0.618
|
SECONDARY outcome
Timeframe: Up to 5 yearsKaplan-Meier curves will be generated for OS. Median OS will be estimated along with 95% confidence intervals using the method of Brookmeyer and Crowley.
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=64 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Overall Survival (OS)
|
11.9 Months
Interval 8.8 to 15.2
|
SECONDARY outcome
Timeframe: Time from enrollment until disease progression or death from any cause, assessed up to 5 yearsKaplan-Meier curves will be generated for PFS. Median PFS will be estimated along with 95% confidence intervals using the method of Brookmeyer and Crowley.
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=64 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Progression Free Survival (PFS)
|
4.1 Months
Interval 2.8 to 6.2
|
SECONDARY outcome
Timeframe: Up to 1 yearThe 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.
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=64 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Disease Control Rate (CR + PR + SD)
|
62.5 percentage of participants
Interval 50.6 to 74.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Exploratory endpoint. Data not collected.
CD8 levels will be correlated with PD-L1 expression using Pearson or Spearman rank correlation coefficients.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsPopulation: Exploratory endpoint. Data not collected.
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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Exploratory outcome. Data not collected.
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).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsPopulation: Exploratory endpoint. Data not collected.
Mass spectrometry-based flow cytometric analysis (CyTOF) will be descriptive based on number and percentage of certain cell populations.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsPopulation: Exploratory endpoint. Data not collected.
Analysis of T-cell receptor repertoire from TILs will be descriptive looking for presence or absence of oligoclonal T-cell population.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsPopulation: Responding patients (CR or PR).
Time from detection of response to disease progression or death, estimated by Kaplan-Meier with 95% confidence interval using the Brookmeyer-Crowley method.
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=14 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Duration of Response
|
11.7 Months
Interval 2.1 to
NA = Upper confidence limit cannot be estimated due to insufficient number of participants with events.
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 30 days after completion of study treatment, maximum of 5 years.Number of patients having any adverse event.
Outcome measures
| Measure |
Treatment (Pembrolizumab)
n=64 Participants
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Incidence of Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
|
64 Participants
|
Adverse Events
Treatment (Pembrolizumab)
Serious events: 25 serious events
Other events: 64 other events
Deaths: 56 deaths
Serious adverse events
| Measure |
Treatment (Pembrolizumab)
n=64 participants at risk
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Endocrine disorders
Adrenal insufficiency
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Immune system disorders
Anaphylaxis
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Blood and lymphatic system disorders
Anemia
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Atrial fibrillation
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Immune system disorders
Autoimmune disorder
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Cardiac arrest
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Colitis
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Psychiatric disorders
Confusion
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Death NOS
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Fatigue
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Fever
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Ileus
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms, benign, malignant, and unspecified - other
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Palpitations
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Pericardial effusion
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Pericardial tamponade
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Renal and urinary disorders
Renal and urinary disorders - other
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - other
|
3.1%
2/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Infections and infestations
Sepsis
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Vascular disorders
Thromboembolic event
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Infections and infestations
Urinary tract infection
|
1.6%
1/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
Other adverse events
| Measure |
Treatment (Pembrolizumab)
n=64 participants at risk
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.
Pembrolizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacogenomic Study: Correlative studies
|
|---|---|
|
Infections and infestations
Upper respiratory infection
|
20.3%
13/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Infections and infestations
Urinary tract infection
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
16/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Investigations
Weight loss
|
15.6%
10/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other
|
14.1%
9/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Constipation
|
34.4%
22/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
29.7%
19/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Psychiatric disorders
Depression
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
16/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Nervous system disorders
Dizziness
|
14.1%
9/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Dry mouth
|
10.9%
7/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Dysphagia
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
40.6%
26/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Edema limbs
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Eye disorders
Eye disorders - Other
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Fatigue
|
75.0%
48/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Fever
|
21.9%
14/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
General disorders and administration site conditions
|
10.9%
7/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
10.9%
7/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
15.6%
10/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Endocrine disorders
Hyperthyroidism
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Endocrine disorders
Hypothyroidism
|
21.9%
14/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Psychiatric disorders
Insomnia
|
20.3%
13/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Localized edema
|
14.1%
9/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Mucositis oral
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Nausea
|
26.6%
17/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Non-cardiac chest pain
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
General disorders
Pain
|
34.4%
22/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Cardiac disorders
Pericardial effusion
|
10.9%
7/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Nervous system disorders
Peripheral motor neuropathy
|
9.4%
6/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
17.2%
11/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
26.6%
17/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic, and mediastinal disorders - Other
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous disorders - Other
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Vascular disorders
Thromboembolic event
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Abdominal pain
|
14.1%
9/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Investigations
Alanine aminotransferase increased
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Investigations
Alkaline phosphatase increased
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
8/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Metabolism and nutrition disorders
Anorexia
|
40.6%
26/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Psychiatric disorders
Anxiety
|
10.9%
7/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Gastrointestinal disorders
Ascites
|
7.8%
5/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Investigations
Aspartate aminotransferase increased
|
14.1%
9/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
4/64 • Up to 30 days after completion of study treatment, maximum of 5 years.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place