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MesotheliomaPhase 1/2NCT05932199

Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma

A Phase 1/2 study testing Durvalumab / tremelimumab and Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab in people with Mesothelioma, run by Baylor College of Medicine at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM. Primary Objectives: The primary objective is to test whether the combination of platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or… 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?
Durvalumab / tremelimumab and Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesUnited States
Study dates
3 Jul 2024to 31 May 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Potentially Surgically resectable MPM. Computed tomography (CT) and positron emission tomography (PET) without disease beyond ipsilateral hemithorax. CT and PET scan without obvious invasion through the chest wall or mediastinum. Surgical evaluation for resectability by an experienced mesothelioma surgeon to assess whether tumor appears resectable on CT and PET. (Final resectability determination is based on intra-operative exploratory thoracotomy to assess chest wall and/or mediastinal invasion that is not apparent based on pre-operative radiological assessment. Given this assessment after enrollment, this determination will be utilized for the safety phase). Based on above criteria, patients will undergo 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 preoperative chest CT and/or PET/CT
  • N2 nodal disease.
  • 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
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  • 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 metastases are present); Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation.
  • Males:
  • 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.
  • The 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.
  • Weight >30 Kg

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 durvalumab.
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) <28 days
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
  • Current or prior use of immunosuppressive medication within 28 days before the infusion with durvalumab or durvalumab + tremelimumab 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.
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  • Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy from diseases other than MPM.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 for disease other than MPM.
  • Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone < 10 mg daily (or equivalent).
  • History of interstitial pneumonitis of autoimmune etiology (including immune checkpoint pneumonitis) which has been symptomatic and/or treatment in the past. Any evidence of current ILD or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • Intolerance of anti- PD-1/PD-L1 or CTLA-4 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
  • Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
  • A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
  • Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
  • Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • History of leptomeningeal carcinomatosis.
  • Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab or + 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.
  • No tissue is obtainable at the time of thoracoscopy.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Robert Ripley, MD contact

713-798-6376

ripley@bcm.edu

United States2 sites, 2 recruiting
  • Duke Cancer Institute

    Durham, North Carolina, 27710

    Jeffrey Clarke, MD, 919-660-9674, Jeffrey.clarke@duke.edu

    Not yet recruiting
  • Baylor St Lukes

    Houston, Texas, 77030

    Monica Vilchis, 713-798-5530, Monica.vilchis@bcm.edu

    Robert Ripley, MD, 713-798-6376, ripley@bcm.edu

    Recruiting

Other trials in United States

About this study

Official title: Combination of Induction Durvalumab and Tremelimumab Alone Versus Durvalumab and Tremelimumab With Chemotherapy for Potentially Resectable Pleural Mesothelioma

Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM.

Primary Objectives:

Read more

The primary objective is to test whether the combination of platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves recurrence-free survival for patients with resectable MPM compared to historical, published data for surgery with chemotherapy.

Secondary Objective(s):

The secondary objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response.

Exploratory Objective(s):

The exploratory objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response for patients with epithelioid and non-epithelioid histologies.

The scientific exploratory objectives include:

  1. Develop an NGS plasma assay of common mutations identified from our previous grant cycle to prospectively measure minimal residual disease (MRD) after resection as a potential, novel biomarker test in mesothelioma.
  2. Determine the predictive role of BH3 profiling in patients undergoing neoadjuvant ICI followed by surgery: With patient samples collected from our neoadjuvant ICI trial, the investigators will test whether BH3 profiling from pre-treatment tumor biopsies and PBMC predicts clinical, radiological, and pathological responses to ICIs. The investigators will identify TAMs from the TiME in MPM tumor samples before and after treatment to compare differences in polarization induced by ICI in clinical and pathologically responding versus non-responding patients.
Read the detailed description

Study Design:

The study will be a two-arm, randomized non-comparative Phase Ib/IIa study of induction dual immunotherapy with durvalumab/tremelimumab OR platinum chemotherapy (cisplatin or carboplatin) and pemetrexed chemotherapy plus dual immunotherapy with durvalumab/tremelimumab for 3 cycles in untreated, potentially resectable malignant pleural mesothelioma for all histologic subtypes and regardless PDL1 score. Patients will continue adjuvant durvalumab for up to 12 months following surgery. Tremelimumab will be given up to cycle 5 on treatment protocol. The investigators will enroll 6 patients to each arm to assess safety and resectability. If differences are not noted between the two arms, the investigators will expand enrollment to 23 patients per arm. To account for up to 10% unevaluable patients, the investigators will enroll at total of 52 patients.

Safety in the first 6 patients in the chemotherapy plus immunotherapy arm will be determined by rate of attempted surgical resection. If 4 or more patients undergo surgical resection, then the study will proceed to enroll the full 23 patient cohort. If 3 or less than 3 patients undergo surgical resection, the study will be paused for PI review of the enrolled patients to determine causality of the safety events.

Conditions
Mesothelioma
Being tested
Durvalumab / tremelimumab, Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab
Medical subject headings
Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab / tremelimumabDrug

    Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL.

    Tremelimumab concentrate for solution for infusion will be supplied in glass vials containing 400 mg or 25 mg tremelimumab at a concentration of 20 mg/mL.

  • Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumabDrug

    Cisplatin 75mg/ m2 (or carboplatin AUC 5-6) + pemetrexed 500 mg/m2 will be provided as per standard of care.

    Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL.

    Tremelimumab concentrate for solution for infusion will be supplied in glass vials containing 400 mg or 25 mg tremelimumab at a concentration of 20 mg/mL.

Study groups in NCT05932199
Study groupRoleWhat they receive
Induction dual immunotherapy with durvalumab / tremelimumabExperimental3 cycles of durvalumab (1500 mg intravenously) + tremelimumab (75 mg intravenously) starting Cycle1 Day (Cohort A).
Receives: Drug: Durvalumab / tremelimumab
Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumabExperimental3 cycles of durvalumab (1500 mg intravenously) + tremelimumab (75 mg intravenously) with cisplatin 75mg/ m2 (or carboplatin AUC 5-6) + pemetrexed 500 mg/m2 (Cohort B).
Receives: Drug: Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrence-free survival of greater than 60% at one year.

    Recurrence-free survival of greater than 60% at one year.

    Measured: Recurrence-free survival of greater than 60% at one year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2023
  2. Study start3 Jul 2024
  3. Primary completion31 May 2028 (estimated)
  4. Study completion31 May 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05932199
Sponsor's protocol ID
H-51512
Status last verified
Sep 2026
First submitted
27 Jun 2023
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab / tremelimumab and Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab in people with Mesothelioma, run by Baylor College of Medicine at 2 sites 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 15 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Monica Vilchis (713-798-5530, monica.vilchis@bcm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free survival of greater than 60% at one year. (time frame: Recurrence-free survival of greater than 60% at one year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 2 Oct 2026.

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