MesotheliomaPhase 2NCT02592551
MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma
A Phase 2 study testing MEDI4736, Tremelimumab and no other name in people with Mesothelioma, run by Baylor College of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mesothelioma
- What is being tested?
- MEDI4736, Tremelimumab and no other name
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2016to 1 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Age >/= 18 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (> 1500 per mm3) Platelet count ≥ 100 × 109/L (>100,000 per mm3) Serum bilirubin ≤ 1.5× institutional upper limit of normal (ULN)AST<3.0 Creatinine clearance >50mL/miN Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if documented liver metastasis are present); Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation;
- Males:
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- Creatinine CL (mL/min) = Weight (kg) × (140 - Age) 72 × serum creatinine (mg/dL)
- Females:
- Creatinine CL (mL/min) = Weight (kg) × (140 - Age) × 0.85 72 × serum creatinine (mg/dL)
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for >/=1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Surgically resectable MPM with no disease extension beyond the ipsilateral hemithorax
- Planned resectional surgery for MPM [extrapleural pneumonectomy (EPP) or pleurectomy and decortication (P/D)]
- Any MPM histology (epithelial, mixed, sarcomatoid)
- N0 or N1 nodal disease as present on perioperative chest CT and/or PET CT.
- N2 nodal disease if no progression after 2 cycles of standard chemotherapy. Progression will be considered if additional N1 or N2 disease develop during chemotherapy
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment or randomization in the present study
- Participation in another clinical study with an investigational product during the last 3 months
- Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug, and 30 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).
- Current or prior use of immunosuppressive medication within 28 days before the infusion with MEDI4736 or MEDI4736 + tremelimumab and through 90 days post infusion, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
- Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy.
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- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to MEDI4736 or any excipient
- History of hypersensitivity to tremelimumab or the combination of MEDI4736 + tremelimumab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 6 months of receiving MEDI4736 or MEDI + tremelimumab
- Receipt of drugs with laxative properties and herbal or natural remedies for constipation within 90 days of receiving MEDI4736 or MEDI + tremelimumab
- Receipt of sunitinib within 3 months of receiving tremelimumab
- Female subjects who are pregnant, breastfeeding, or male or female subjects of reproductive potential who are not employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with the evaluation of the study treatment or interpretation of subject safety or study results
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
- Subjects with uncontrolled seizures
- N3 nodal disease
- History of interstitial lung disease/pneumonitis
- No tissue is obtainable at the time of thoracoscopy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Window Of Opportunity Phase II Study Of MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma
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.
Read the detailed description
Subjects with MPM will undergo surgical mediastinal lymph node biopsy (cervical mediastinoscopy) and simultaneous surgical biopsy of the pleural tumor by thoracoscopy, at which time tumor tissue (at least 2 g) and peripheral blood will be collected for the study. These procedures are performed as standard of care in the treatment of these subjects. The subject will be randomized. Three days to three weeks after the biopsy, subjects will be randomly treated with either MEDI-4736 (15 mg/kg once intravenously) or MEDI-4736 (1500 mg once intravenously) plus tremelimumab (75 mg once intravenously) or a control group in a randomized controlled study design. There will be two treatment arms (MEDI4736 only and combination MEDI4736+tremelimumab) and one untreated arm (control). Randomization, stratified by receiving previous chemotherapy or not, will be performed and will help to minimize patient selection biases between three arms. Subjects under 30 kg will be treated with weight-based dosing for both MEDI4736 and Tremelimumab combination therapy. These patients are excluded from fixed based dosing to limit endotoxin exposure from the drug preparations. One to six weeks after the infusion, subjects will undergo resectional surgery, including extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), at which time the tumor will be removed (typically 200-1000 g) and obtained for study. Four patients that do not undergo treatment with MEDI-4736 or tremelimumab will be included as controls. Blood will be obtained after the induction of general anesthesia for both the thoracoscopy procedure and the EPP or P/D resectional procedure, as is routinely done in these procedures. The sixth rib will be obtained at the time of the resection. After the removal of the tumor, standard protocol includes intraoperative heated chemotherapy using a lavage of intracavitary cisplatin in the presence of conserved renal function (Sugarbaker et al., 2013, 2014; Richards et al., 2006).
- Conditions
- Mesothelioma
- Being tested
- MEDI4736, Tremelimumab, no other name
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Drug
Also called durvalumab
MEDI4736 is formulated at 50 mg/mL in 26 mM histidine/histidine-HCl, 275 mM trehalose dihydrate, 0.02% (w/v) polysorbate 80, pH 6.0.
TremelimumabDrug
Also called no other name
Tremelimumab Drug Product is formulated at a nominal concentration of 20 mg/mL in 20 mM histidine/histidine hydrochloride, 222 mM trehalose dihydrate, 0.02% (weight/volume [w/v]) polysorbate 80, 0.27 mM disodium edetate dihydrate (EDTA), pH 5.5.
no other nameOther
Neither MEDI4736 nor Tremelimumab will be used.
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 | Experimental | 8 patients will receive an infusion of MEDI4736 (15 mg/kg intravenously, once), one to six weeks prior to surgical resection. Receives: Drug: MEDI4736 |
| MEDI4736 + Tremelimumab | Active comparator | 8 patients will receive an infusion of MEDI4736 (1500 mg intravenously, once) + tremelimumab (75mg intravenously, once), one to six weeks prior to surgical resection. Receives: Drug: MEDI4736; Drug: Tremelimumab |
| Untreated arm (control) | Placebo comparator | 4 patients will not receive MEDI4736 or Tremelimumab. Receives: Other: no other name |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg)
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.
Measured: at day 1 after screening and at a surgery within one to six weeks after treatment
Secondary outcomes (10)
Change in Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells.
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.
Measured: at day 1 after screening and at a surgery within one to six weeks after treatment
Change in Tumor Expression Programmed Death-ligand 1 (PD-L1).
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.
Measured: at day 1 after screening and at a surgery within one to six weeks after treatment
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.
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.
Measured: at a surgery within one to six weeks after treatment
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.
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.
Measured: the untreated group(control) : at day 1, MEDI4736 + Tremelimumab: at a surgery within one to six weeks after treatment (MEDI4736+Tremelimumab) group
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
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.
Measured: at a surgery within one to six weeks after treatment
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.
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.
Measured: Untreated group (control): at day 1, MEDI-4736 and Tremelimumab group: at a surgery within one to six weeks after treatment
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.
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.
Measured: at a surgery within one to six weeks after treatment
Tumor Expression Programmed Death-ligand 1 (PD-L1) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Untreated Patients.
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.
Measured: Untreated arm (control): at day 1 after screening, MEDI4736 + Tremelimumab group: at a surgery within one to six weeks after treatment
Median Recurrence-free Survival (RFS)
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.
Measured: Participants will be followed up until disease recurrence or censor for 2 year after surgery
Median Overall Survival (OS)
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.
Measured: Participants will be followed up until death or censor for 2 year after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2015 (estimated)
- Study start11 May 2016
- Primary completion6 Aug 2019
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bryan Burt, MD, Baylor College of Medicine
- Investigators
- Bryan Burt, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02592551
- Sponsor's protocol ID
- H-36952
- Status last verified
- Sep 2022
- First submitted
- 19 Oct 2015
- Last updated
- 29 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mitra S, Jang HJ, Kuncheria A, Kang SW, Choi JM, Shim JS, Lee C, Ranchod P, Jindra P, Ramineni M, Patel M, Ripley RT, Groth SS, Blackmon SH, Burt BM, Lee HS. Soluble mesothelin-related peptide as a prognosticator in pleural mesothelioma patients receiving checkpoint immunotherapy. J Thorac Cardiovasc Surg. 2025 Apr;169(4):1082-1095.e4. doi: 10.1016/j.jtcvs.2024.10.005. Epub 2024 Oct 10.
PubMed 39395787Lee HS, Jang HJ, Ramineni M, Wang DY, Ramos D, Choi JM, Splawn T, Espinoza M, Almarez M, Hosey L, Jo E, Hilsenbeck S, Amos CI, Ripley RT, Burt BM. A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2023 Feb 1;29(3):548-559. doi: 10.1158/1078-0432.CCR-22-2566.
PubMed 36469573
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window Of Opportunity Phase II Study Of MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT02592551
- Acronym / sponsor ID
- H-36952
- Conditions
- Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 11 May 2016 (actual)
- Primary completion
- 6 Aug 2019 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 30 Oct 2015 (estimated)
- Results
- Posted 13 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjects with MPM will undergo surgical mediastinal lymph node biopsy (cervical mediastinoscopy) and simultaneous surgical biopsy of the pleural tumor by thoracoscopy, at which time tumor tissue (at least 2 g) and peripheral blood will be collected for the study. These procedures are performed as standard of care in the treatment of these subjects. The subject will be randomized. Three days to three weeks after the biopsy, subjects will be randomly treated with either MEDI-4736 (15 mg/kg once intravenously) or MEDI-4736 (1500 mg once intravenously) plus tremelimumab (75 mg once intravenously) or a control group in a randomized controlled study design. There will be two treatment arms (MEDI4736 only and combination MEDI4736+tremelimumab) and one untreated arm (control). Randomization, stratified by receiving previous chemotherapy or not, will be performed and will help to minimize patient selection biases between three arms. Subjects under 30 kg will be treated with weight-based dosing for both MEDI4736 and Tremelimumab combination therapy. These patients are excluded from fixed based dosing to limit endotoxin exposure from the drug preparations. One to six weeks after the infusion, subjects will undergo resectional surgery, including extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), at which time the tumor will be removed (typically 200-1000 g) and obtained for study. Four patients that do not undergo treatment with MEDI-4736 or tremelimumab will be included as controls. Blood will be obtained after the induction of general anesthesia for both the thoracoscopy procedure and the EPP or P/D resectional procedure, as is routinely done in these procedures. The sixth rib will be obtained at the time of the resection. After the removal of the tumor, standard protocol includes intraoperative heated chemotherapy using a lavage of intracavitary cisplatin in the presence of conserved renal function (Sugarbaker et al., 2013, 2014; Richards et al., 2006).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 | Experimental | Drug: MEDI47368 patients will receive an infusion of MEDI4736 (15 mg/kg intravenously, once), one to six weeks prior to surgical resection. |
| MEDI4736 + Tremelimumab | Active comparator | Drug: MEDI4736, Drug: Tremelimumab8 patients will receive an infusion of MEDI4736 (1500 mg intravenously, once) + tremelimumab (75mg intravenously, once), one to six weeks prior to surgical resection. |
| Untreated arm (control) | Placebo comparator | Other: no other name4 patients will not receive MEDI4736 or Tremelimumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Age >/= 18 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (> 1500 per mm3) Platelet count ≥ 100 × 109/L (>100,000 per mm3) Serum bilirubin ≤ 1.5× institutional upper limit of normal (ULN)AST<3.0 Creatinine clearance >50mL/miN Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if documented liver metastasis are present); Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation;
Key exclusion criteria (26 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment or randomization in the present study
- Participation in another clinical study with an investigational product during the last 3 months
- Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug, and 30 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).
- Current or prior use of immunosuppressive medication within 28 days before the infusion with MEDI4736 or MEDI4736 + tremelimumab and through 90 days post infusion, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI4736Also: durvalumabMEDI4736 is formulated at 50 mg/mL in 26 mM histidine/histidine-HCl, 275 mM trehalose dihydrate, 0.02% (w/v) polysorbate 80, pH 6.0. | Drug | MEDI4736, MEDI4736 + Tremelimumab |
| TremelimumabAlso: no other nameTremelimumab Drug Product is formulated at a nominal concentration of 20 mg/mL in 20 mM histidine/histidine hydrochloride, 222 mM trehalose dihydrate, 0.02% (weight/volume [w/v]) polysorbate 80, 0.27 mM disodium edetate dihydrate (EDTA), pH 5.5. | Drug | MEDI4736 + Tremelimumab |
| no other nameNeither MEDI4736 nor Tremelimumab will be used. | Other | Untreated arm (control) |
Primary outcome
Change in Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg)
Time frame: 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.
10 secondary outcomes
Change in Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells.
Time frame: at day 1 after screening and at a surgery within one to six weeks after treatment
Change in Tumor Expression Programmed Death-ligand 1 (PD-L1).
Time frame: at day 1 after screening and at a surgery within one to six weeks after treatment
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.
Time frame: at a surgery within one to six weeks after treatment
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.
Time frame: the untreated group(control) : at day 1, MEDI4736 + Tremelimumab: at a surgery within one to six weeks after treatment (MEDI4736+Tremelimumab) group
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
Time frame: at a surgery within one to six weeks after treatment
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.
Time frame: Untreated group (control): at day 1, MEDI-4736 and Tremelimumab group: at a surgery within one to six weeks after treatment
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.
Time frame: at a surgery within one to six weeks after treatment
Tumor Expression Programmed Death-ligand 1 (PD-L1) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Untreated Patients.
Time frame: Untreated arm (control): at day 1 after screening, MEDI4736 + Tremelimumab group: at a surgery within one to six weeks after treatment
Median Recurrence-free Survival (RFS)
Time frame: Participants will be followed up until disease recurrence or censor for 2 year after surgery
Median Overall Survival (OS)
Time frame: Participants will be followed up until death or censor for 2 year after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39395787Mitra S, Jang HJ, Kuncheria A, Kang SW, Choi JM, Shim JS, Lee C, Ranchod P, Jindra P, Ramineni M, Patel M, Ripley RT, Groth SS, Blackmon SH, Burt BM, Lee HS. Soluble mesothelin-related peptide as a prognosticator in pleural mesothelioma patients receiving checkpoint immunotherapy. J Thorac Cardiovasc Surg. 2025 Apr;169(4):1082-1095.e4. doi: 10.1016/j.jtcvs.2024.10.005. Epub 2024 Oct 10.
- Derived from this study: PubMed 36469573Lee HS, Jang HJ, Ramineni M, Wang DY, Ramos D, Choi JM, Splawn T, Espinoza M, Almarez M, Hosey L, Jo E, Hilsenbeck S, Amos CI, Ripley RT, Burt BM. A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2023 Feb 1;29(3):548-559. doi: 10.1158/1078-0432.CCR-22-2566.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan Burt, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MEDI4736, Tremelimumab and no other name in people with Mesothelioma, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) (time frame: at day 1 after screening and at a surgery within one to six weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02592551, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.