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NCT02592551

MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma

Completed Phase 2 Results posted Last updated 29 September 2022
What this trial tests

Phase 2 trial testing MEDI4736 in Mesothelioma in 24 participants. Completed in 1 September 2022.

Timeline
11 May 2016
Primary endpoint
6 August 2019
1 September 2022

Quick facts

Lead sponsorBaylor College of Medicine
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposeother
Enrollment24
Start date11 May 2016
Primary completion6 August 2019
Estimated completion1 September 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Baylor College of Medicine

Who can join

18 and older, any sex, with Mesothelioma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) Primary · at day 1 after screening and at a surgery within one to six weeks after treatment

Tissue biomarker immune response of CD8 and Treg to before and after MEDI-4736 and Tremelimumab will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The ratios of CD8/Treg are calculated by diving CD8 by Treg.

GroupValue95% CI
MEDI4736 + Tremelimumab8.6-1.4 – 29.9
Change in Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells. Secondary · at day 1 after screening and at a surgery within one to six weeks after treatment

Tissue biomarker for the immune response of ICOS+ CD4 T cells to before and after MEDI-4736 and Tremelimumab will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The percentages of ICOS+CD4 T cells are calculated by dividing by total cells.

GroupValue95% CI
MEDI4736 + Tremelimumab-2.1-5.2 – 1
Change in Tumor Expression Programmed Death-ligand 1 (PD-L1). Secondary · at day 1 after screening and at a surgery within one to six weeks after treatment

Tumor expression programmed death-ligand 1 (PD-L1) before and after treatment with combination MEDI-4736 and Tremelimumab will be obtained by immunohistochemistry and CytoF. The unit of measure is MMI. MMI (mean metal intensity or mean mass intensity) is a signal intensity in time-of-flight mass cytometry (CyTOF), which is the same as MFI (mean fluorescent intensity) in flow cytometry. Mean metal intensity looks more common in CyTOF to tell it from the unit in mass spectrometry. Its range is from 0 to infinity.

GroupValue95% CI
MEDI4736 + Tremelimumab0.07-0.12 – 0.30
Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Patients Treated With MEDI-4736 Alone. Secondary · at a surgery within one to six weeks after treatment

Tissue biomarker immune response of CD8 and Treg after MEDI-4736 and Tremelimumab, and after MEDI4736 alone will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The ratios of CD8/Treg are calculated by diving CD8 by Treg.

GroupValue95% CI
MEDI473683.4 – 9.4
MEDI4736 + Tremelimumab9.72 – 20.9
Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and Untreated Patients. Secondary · the untreated group(control) : at day 1, MEDI4736 + Tremelimumab: at a surgery within one to six weeks after treatment (MEDI4736+Tremelimumab) group

Tissue biomarker immune response of CD8 and Treg after MEDI-4736 and Tremelimumab, and at day 1 of untread will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The ratios of CD8/Treg are calculated by diving CD8 by Treg.

GroupValue95% CI
MEDI4736 + Tremelimumab9.72 – 20.9
Untreated Arm (Control)4.032.7 – 12.6
Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Patients Treated With MEDI-4736 Alone Secondary · at a surgery within one to six weeks after treatment

Tissue biomarker immune response of ICOS+ CD4 T cells after combination therapy (MEDI-4736 and Tremelimumab) and after MEDI4736 alone will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The percentages of ICOS+CD4 T cells are calculated by dividing by total cells.

GroupValue95% CI
MEDI47361.20.5 – 3.9
MEDI4736 + Tremelimumab4.52.5 – 6.5
Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Untreated Patients. Secondary · Untreated group (control): at day 1, MEDI-4736 and Tremelimumab group: at a surgery within one to six weeks after treatment

Tissue biomarker immune response of ICOS+ CD4 T cells after combination therapy (MEDI-4736 and Tremelimumab) and after untreated patients will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The percentages of ICOS+CD4 T cells are calculated by dividing by total cells.

GroupValue95% CI
MEDI4736 + Tremelimumab4.52.5 – 6.5
Tumor Expression Programmed Death-ligand 1 (PD-L1) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Patients Treated With MEDI-4736 Alone. Secondary · at a surgery within one to six weeks after treatment

Tumor expression programmed death-ligand 1 (PD-L1) after combination therapy (MEDI-4736 and Tremelimumab) and after MEDI-4736 alone will be obtained by immunohistochemistry and CytoF. The unit of measure is MMI. MMI (mean metal intensity or mean mass intensity) is a signal intensity in time-of-flight mass cytometry (CyTOF), which is the same as MFI (mean fluorescent intensity) in flow cytometry. Mean metal intensity looks more common in CyTOF to tell it from the unit in mass spectrometry. Its range is from 0 to infinity.

GroupValue95% CI
MEDI47360.310.19 – 0.69
MEDI4736 + Tremelimumab0.180.12 – 0.59
Tumor Expression Programmed Death-ligand 1 (PD-L1) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Untreated Patients. Secondary · Untreated arm (control): at day 1 after screening, MEDI4736 + Tremelimumab group: at a surgery within one to six weeks after treatment

Tumor expression programmed death-ligand 1 (PD-L1) after combination therapy (MEDI-4736 and Tremelimumab) and before and at day 1 of untreate alone will be obtained by immunohistochemistry and CytoF. The unit of measure is MMI. MMI (mean metal intensity or mean mass intensity) is a signal intensity in time-of-flight mass cytometry (CyTOF), which is the same as MFI (mean fluorescent intensity) in flow cytometry. Mean metal intensity looks more common in CyTOF to tell it from the unit in mass spectrometry. Its range is from 0 to infinity.

GroupValue95% CI
MEDI4736 + Tremelimumab0.180.12 – 0.59
Untreated Arm (Control)0.240.11 – 1.08
Median Recurrence-free Survival (RFS) Secondary · Participants will be followed up until disease recurrence or censor for 2 year after surgery

RFS based on the Kaplan-Meier method is defined as the time between treatment and disease recurrence or censored and participants in either MEDI-4736 alone or MEDI-4736 plus Tremelimumab will be followed up for 2 years after surgery.

GroupValue95% CI
MEDI4736143.2 – NA
MEDI4736 + TremelimumabNA1.6 – NA
Median Overall Survival (OS) Secondary · Participants will be followed up until death or censor for 2 year after surgery

OS based on the Kaplan-Meier method is defined as the time between treatment and death or censored and participants in either MEDI-4736 alone or MEDI-4736+Tremelimumab will be followed up for 2 years after surgery.

GroupValue95% CI
MEDI473614.41 – 27
MEDI4736 + TremelimumabNA5.0 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were assessed by the study schedule on the day of infusion and followed up until 4 weeks after hospital discharge, the maximum duration of 24 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MEDI4736
Serious: 4/9 (44%)
Deaths: 7/9
MEDI4736 + Tremelimumab
Serious: 4/11 (36%)
Deaths: 6/11
Untreated Arm (Control)
Serious: 1/4 (25%)
Deaths: 3/4

Serious adverse events (21 terms)

ReactionSystemMEDI4736MEDI4736 + TremelimumabUntreated Arm (Control)
Death NOSGeneral disorders
Acute coronary syndromeCardiac disorders
Heart failureCardiac disorders
Myocardial infarctionCardiac disorders
Edema limbsGeneral disorders
FatigueGeneral disorders
Multi-organ failureGeneral disorders
PainGeneral disorders
Sudden death NOSGeneral disorders
Hepatobiliary disorders - Other, specifyHepatobiliary disorders
FallInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Weight lossInvestigations
AnorexiaMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
SyncopeNervous system disorders
Acute kidney injuryRenal and urinary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Rash acneiformSkin and subcutaneous tissue disorders
HypotensionVascular disorders
Other adverse events (59 terms — click to expand)

ReactionSystemMEDI4736MEDI4736 + TremelimumabUntreated Arm (Control)
HyperglycemiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
HypotensionVascular disorders
Edema limbsGeneral disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
Weight lossInvestigations
AnorexiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
Chest wall painMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Sinus bradycardiaCardiac disorders
Supraventricular tachycardiaCardiac disorders
Ventricular arrhythmiaCardiac disorders
Ventricular tachycardiaCardiac disorders
Abdominal painGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Salivary duct inflammationGastrointestinal disorders
FeverGeneral disorders
Mucosal infectionInfections and infestations
Skin infectionInfections and infestations
Activated partial thromboplastin time prolongedInvestigations
Blood bilirubin increasedInvestigations
Fibrinogen decreasedInvestigations
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
Urine output decreasedInvestigations
Weight gainInvestigations
White blood cell decreasedInvestigations
AcidosisMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders

Most-reported serious reactions: Death NOS, Acute coronary syndrome, Heart failure, Myocardial infarction, Edema limbs, Fatigue, Multi-organ failure, Pain.

Data from ClinicalTrials.gov NCT02592551 adverse events section.

Sponsor's own description

The objective of this study is to determine whether MEDI4736 or combination therapy with MEDI4736 + tremelimumab are associated with favorable alterations of the intratumoral immunologic environment in subjects undergoing resectional surgery for Malignant Pleural Mesothelioma MPM.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Other trials of MEDI4736

Trials testing the same drug.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing