DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma

NCT04334759 | Completed Phase 3 DMC FDA Drug

• 4 other identifiers: DREAM3RPrE0506TOGA 18/001CTC 0231
• Study Type: interventional
• Target: 214
• Locations: 3 countries
• Sites: 57

Brief Summary

Patients with pleural mesothelioma (PM) that cannot be surgically removed will receive standard chemotherapy (cisplatin or carboplatin and pemetrexed) given with durvalumab, a type of immunotherapy, or a treatment chosen by the study doctor, which is either standard chemotherapy or immunotherapy combination (ipilimumab and nivolumab). Durvalumab is an antibody (a type of human protein) that works by blocking a body substance called Programmed Death-Ligand 1 (PD-L1). Blocking PD-L1 helps the body's immune system attack cancer cells. Research has shown that durvalumab can slow tumor growth and shrink tumors in some people with cancer. Previous studies of combining durvalumab and chemotherapy showed that this combination is active in advanced mesothelioma. The purpose of this study is to see whether adding durvalumab to standard chemotherapy will improve overall survival (OS) in patients with PM.

Conditions

Mesothelioma; Pleural Mesothelioma; Malignant Pleural Mesothelioma

Keywords

Unresectable Mesothelioma; Durvalumab; Anti-Programmed Death-Ligand 1 Antibody; Immune Checkpoint Inhibitor; Ipilimumab; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Effects on Overall Survival

  Defined as the time from randomisation to the date of death due to any cause.

  Minimum follow-up is 24 months after randomisation.

Secondary Outcomes (9)

• Progression-Free Survival (PFS)

  Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression (minimum follow-up is 24 months after randomisation).

• Objective Tumour Response Rate (OTRR)

  Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression (minimum follow-up is 24 months after randomisation).

• Classify and grade participants adverse events as assessed by CTCAE V5.0

  90 days after last dose of immunotherapy or 30 days after last dose of chemotherapy, whichever is longer.

• Health-Related Quality of Life (QOL): QLQ-C30

  Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50, then every 12 weeks until disease progression and at first progression visit (minimum follow-up is 24 months after randomisation).

• Health-Related QOL: LC29

  Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50, then every 12 weeks until disease progression and at first progression visit (minimum follow-up is 24 months after randomisation).

Study Arms (3)

Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance

EXPERIMENTAL

Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab

Drug: Durvalumab

Control Arm: Chemotherapy, then Observation

ACTIVE COMPARATOR

Standard Chemotherapy for 4 to 6 cycles, followed by Observation

Drug: Standard Chemotherapy

Control Arm: Ipilimumab and Nivolumab

ACTIVE COMPARATOR

Ipilimumab every 6 weeks and Nivolumab every 2 or 3 weeks for up to 2 years.

Drug: Ipilimumab and Nivolumab

Interventions

Durvalumab DRUG

Durvalumab 1500 milligrams (mg) intravenous (IV) every 3 weeks + Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks for 4 to 6 cycles, followed by maintenance with Durvalumab 1500 mg IV every 4 weeks

Also known as: MEDI4736, Imfinzi

Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance

Standard Chemotherapy DRUG

Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks) for 4 to 6 cycles, followed by Observation

Also known as: Cisplatin or Carboplatin and Pemetrexed

Control Arm: Chemotherapy, then Observation

Ipilimumab and Nivolumab DRUG

Ipilimumab 1 mg/kg every 6 weeks and Nivolumab 360 mg every 3 weeks or 3 mg/kg every 2 weeks for up to 2 years

Also known as: Yervoy, Opdivo

Control Arm: Ipilimumab and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18 years or over) with a histological diagnosis of epithelioid pleural mesothelioma that is not amenable to curative surgical resection. Histological diagnosis requires tumour tissue from an open biopsy, or a core biopsy with a needle of 19 gauge or wider.
• Measurable disease as per modified RECIST 1.1 (mRECIST 1.1) criteria for assessment of response in pleural mesothelioma, without prior radiotherapy to these sites.
• Body weight \>30 kg,
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Tumour tissue (Formalin-Fixed Paraffin-Embedded \[FFPE\]) available from standard of care diagnostic biopsy for PD-L1 testing and other correlative biomarker testing at a central laboratory.
• Life expectancy of at least 12 weeks.
• Adequate blood tests (done within 14 days prior to randomisation) and with values within the ranges specified below. Blood transfusions are permissible if completed at least 7 days prior to treatment start.
• Haemoglobin ≥ 9.0 g/L
• Absolute neutrophil count ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except participants with Gilbert's Syndrome, who are eligible with bilirubin ≤ 2.5 ULN)
• Alanine transaminase ≤ 2.5 x upper limit of normal (ULN), unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
• Aspartate aminotransferase ≤ 2.5 x ULN, unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
• Creatinine clearance (CrCl) ≥ 45 mL/min (Cockcroft-Gault formula). NOTE: Carboplatin AUC 5 must be the initial platinum agent of choice in patients with creatinine Cl \<60 mL/min but ≥ 45 mL/min, or those with clinically reported hearing loss.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient or legal representative must sign a consent form prior to enrolment in the trial to document their willingness to participate.

You may not qualify if:

• Non-epithelioid histology (biphasic or sarcomatoid).
• Prior chemotherapy or other systemic anti-cancer or immunotherapy for PM.
• Diagnosis based only on cytology or aspiration biopsy with a needle narrower than 19 gauge.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g. colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included
• Patients with celiac disease controlled by diet alone
• Any condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab or ipilimumab or nivolumab administration. Intranasal, inhaled or topical steroids or local steroid injections (e.g. intra-articular injection) are permitted in the absence of active autoimmune disease. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
• Participants with symptomatic or uncontrolled brain metastases or leptomeningeal disease are excluded.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• Current treatment or treatment within the last 12 months with any investigational anti-cancer products.
• Concurrent enrolment in another clinical study testing an anticancer treatment.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Thoracic Oncology Group Australasia (TOGA): collaborator
• University of Sydney: collaborator
• PrECOG, LLC.: lead

Study Sites (57)

University of California San Diego

La Jolla, California, 92093, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 18054, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

NorthShore University Health System/Kellogg Cancer Center

Evanston, Illinois, 60201, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massaschusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Morristown Medical/Atlantic Health

Morristown, New Jersey, 07960, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Abramson Cancer Cener at Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Wyong Hospital

Hamlyn Terrace, New South Wales, 2259, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Orange Health Service

Orange, New South Wales, 2800, Australia

Location

Northern Cancer Institute (GenesisCare)

Saint Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Icon Cancer Care Wesley

Auchenflower, Queensland, 4066, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Icon Cancer Care Chermside

Chermside, Queensland, 4032, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Townsville University Hospital

Douglas, Queensland, 4814, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Epworth HealthCare - Richmond

Richmond, Victoria, 3121, Australia

Location

Sunshine Hospital (Western Health)

Saint Albans, Victoria, 3021, Australia

Location

Goulburn Valley Health

Shepparton, Victoria, 3630, Australia

Location

Sir Charles Gairdner Hospital (SCGH)

Nedlands, Western Australia, 6009, Australia

Location

Auckland City Hospital

Grafton, Auckland, 1023, New Zealand

Location

Related Publications (3)

• Kok PS, Forde PM, Hughes B, Sun Z, Brown C, Ramalingam S, Cook A, Lesterhuis WJ, Yip S, O'Byrne K, Pavlakis N, Brahmer J, Anagnostou V, Ford K, Fitzpatrick K, Bricker A, Cummins MM, Stockler M, Nowak AK; Thoracic Oncology Group of Australasia (TOGA) and PrECOG, USA. Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial. BMJ Open. 2022 Jan 25;12(1):e057663. doi: 10.1136/bmjopen-2021-057663.

  PMID: 35078853 BACKGROUND

• Kindler HL. Understanding the new therapeutic options for mesothelioma. Lancet Oncol. 2021 Oct;22(10):1353-1355. doi: 10.1016/S1470-2045(21)00520-9. Epub 2021 Sep 6. No abstract available.

  PMID: 34499875 DERIVED

• Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.

  PMID: 33358660 DERIVED

MeSH Terms

Conditions

Mesothelioma; Mesothelioma, Malignant

Interventions

durvalumab; Cisplatin; Carboplatin; Pemetrexed; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Forde, MD

  Johns Hopkins University

  STUDY CHAIR

• Anna Nowak, MD

  Faculty of Health and Medical Sciences University of Western Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: First-line chemotherapy with cisplatin or carboplatin and pemetrexed + durvalumab OR physician's choice of either first-line chemotherapy alone, or ipilimumab and nivolumab.

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: February 18, 2021
• Primary Completion: June 20, 2025
• Study Completion: June 30, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); AU (31); US (25)