MesotheliomaPhase 3DREAM3RNCT04334759
DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
A Phase 3 study testing Durvalumab, Standard Chemotherapy and Ipilimumab and Nivolumab in people with Mesothelioma and Pleural Mesothelioma, run by PrECOG, LLC. at 57 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma, Pleural Mesothelioma, Malignant Pleural Mesothelioma
- What is being tested?
- Durvalumab, Standard Chemotherapy and Ipilimumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 57 sitesin 3 countries
- Study dates
- 18 Feb 2021to 30 Jun 2025
- Phase
- Phase 3
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
- Women of childbearing potential must use a reliable means of contraception during treatment and for at least 90 days thereafter. Breastfeeding is not permissible during or for at least 90 days after the final study treatment. Men must have been surgically sterilised or use a barrier method of contraception if they are sexually active with a woman of child bearing potential.
- Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
Who cannot join
- 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
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- 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.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment on protocol. Note: Local surgery of isolated lesions for palliative intent is acceptable. Limited pleural biopsy procedures do not apply.
- No other malignancy that requires active treatment. Participants with a past history of adequately treated carcinoma in situ, non-melanoma skin cancer or lentigo maligna without evidence of disease or superficial transitional cell carcinoma of the bladder are eligible.
- Hearing loss or peripheral neuropathy considered by the investigators to contraindicate administration of either cisplatin, carboplatin or pemetrexed.
- History of allergy or hypersensitivity to investigational product, cisplatin, carboplatin, pemetrexed, ipilimumab, nivolumab or any excipient.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive cardiac failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, active peptic ulcer disease or gastritis, serious chronic gastrointestinal conditions associated with diarrhoea, active bleeding diatheses.
- Hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Exceptions include past or resolved Hepatitis B (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) and patients positive for hepatitis C (HCV) antibody if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in absence of clinical suspicion of HIV.
- Known history of primary immunodeficiency, allogeneic organ transplant, pneumonitis or active tuberculosis.
- Receipt of live attenuated vaccination within 30 days prior to enrolment or within 30 days of receiving durvalumab, ipilimumab, nivolumab.
- Specific comorbidities or conditions or concomitant medications which may interact with the investigational product(s).
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
- Serious medical or psychiatric conditions or social situation that might limit compliance with study requirements, substantially increase risk of incurring adverse events or compromise the ability of the patient to give written informed consent.
Trial locations and contacts
57 sites in 3 countries.
57 sites in 3 countries
Australia31 sites
Icon Cancer Care Wesley
Auchenflower, Queensland, 4066
Flinders Medical Centre
Bedford Park, South Australia, 5042
Sunshine Coast University Hospital
Birtinya, Queensland, 4575
Blacktown Hospital
Blacktown, New South Wales, 2148
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Icon Cancer Care Chermside
Chermside, Queensland, 4032
The Prince Charles Hospital
Chermside, Queensland, 4032
Monash Health
Clayton, Victoria, 3168
Coffs Harbour Health Campus
Coffs Harbour, New South Wales, 2450
Townsville University Hospital
Douglas, Queensland, 4814
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, 3199
Canberra Hospital
Garran, Australian Capital Territory, 2605
Gosford Hospital
Gosford, New South Wales, 2250
Wyong Hospital
Hamlyn Terrace, New South Wales, 2259
Austin Hospital
Heidelberg, Victoria, 3084
Royal Hobart Hospital
Hobart, Tasmania, 7000
Nepean Hospital
Kingswood, New South Wales, 2747
Launceston General Hospital
Launceston, Tasmania, 7250
Liverpool Hospital
Liverpool, New South Wales, 2170
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Sir Charles Gairdner Hospital (SCGH)
Nedlands, Western Australia, 6009
Orange Health Service
Orange, New South Wales, 2800
Epworth HealthCare - Richmond
Richmond, Victoria, 3121
Sunshine Hospital (Western Health)
Saint Albans, Victoria, 3021
Northern Cancer Institute (GenesisCare)
Saint Leonards, New South Wales, 2065
Goulburn Valley Health
Shepparton, Victoria, 3630
Icon Cancer Care South Brisbane
South Brisbane, Queensland, 4101
Calvary Mater Newcastle
Waratah, New South Wales, 2298
Westmead Hospital
Westmead, New South Wales, 2145
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
United States25 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Massaschusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22903
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
NorthShore University Health System/Kellogg Cancer Center
Evanston, Illinois, 60201
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Baylor College of Medicine
Houston, Texas, 77030
MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Diego
La Jolla, California, 92093
University of Miami
Miami, Florida, 33136
Morristown Medical/Atlantic Health
Morristown, New Jersey, 07960
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Memorial Sloan Kettering
New York, New York, 10065
Abramson Cancer Cener at Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
Allegheny Cancer Center
Pittsburgh, Pennsylvania, 15224
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416
Moffitt Cancer Center
Tampa, Florida, 18054
About this study
Official title: DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial
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.
Read the detailed description
Mesothelioma is a malignant tumor of the mesothelial surfaces primarily arising in the thoracic pleura. In the United Kingdom and USA the expected number of cases in the next few decades are 65,000 and 85,000, respectively. Once diagnosed, this disease is rarely cured with a median survival of less than a year.
This is an International, Open-Label, Multi-center, Phase III study. Patients will be randomized 1:1 to receive (a) chemotherapy given with durvalumab versus (b) physician's choice of either chemotherapy alone, or ipilimumab and nivolumab.
Experimental Arm:
- Durvalumab every 3 weeks + standard chemotherapy (cisplatin or carboplatin every 3 weeks + pemetrexed every 3 weeks) for 4 to 6 cycles, followed by durvalumab every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal.
Control Arm: Physician Choice
- Standard chemotherapy (cisplatin or carboplatin every 3 weeks + pemetrexed every 3 weeks) for 4 to 6 cycles followed by observation
- Ipilimumab every 6 weeks and nivolumab every 2 or 3 weeks [physician discretion] for up to 2 years until disease progression, unacceptable toxicity or patient withdrawal .
Tumor assessments and Quality of Life (QOL) forms will be performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression. The QOL forms will also be repeated during the first visit after progression.
Mandatory pre-treatment tumor tissue sample (i.e., obtained during a previous procedure or biopsy) for research will also be required. Blood samples for research at 3 time points will be done.
The study is being led jointly by PrECOG as the US sponsor and University of Sydney as the international sponsor.
- Being tested
- Durvalumab, Standard Chemotherapy, Ipilimumab and Nivolumab
- Keywords
- Unresectable Mesothelioma, Durvalumab, Anti-Programmed Death-Ligand 1 Antibody, Immune Checkpoint Inhibitor, Ipilimumab, Nivolumab
- Medical subject headings
- Mesothelioma, Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736, Imfinzi
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
Standard ChemotherapyDrug
Also called Cisplatin or Carboplatin and Pemetrexed
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
Ipilimumab and NivolumabDrug
Also called Yervoy, Opdivo
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
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance | Experimental | Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab Receives: Drug: Durvalumab |
| Control Arm: Chemotherapy, then Observation | Active comparator | Standard Chemotherapy for 4 to 6 cycles, followed by Observation Receives: 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. Receives: Drug: Ipilimumab and Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Overall Survival (OS)
OS based on the Kaplan-Meier method is defined as the duration from randomisation to the date of death due to any cause, or is censored at date last known alive.
Measured: Minimum follow-up is 24 months after randomisation. Median follow-up for survival is of 33 months with range (3 months - 47 months).
Secondary outcomes (5)
Median Progression-Free Survival (PFS)
PFS based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) defined per modified RECIST 1.1 for PM and iRECIST, or death, or is censored at time of last disease assessment.
Measured: Disease was evaluated at baseline, 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). Median follow-up for survival is of 33 months with range (3 months - 47 months).
Objective Tumour Response Rate (OTRR)
Objective tumour response rate (OTRR) is defined as the proportion of participants with a documented complete response, partial response (CR + PR) based on iRECIST criteria.
Measured: Disease was evaluated 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). The treatment duration ranged from 0 to 36 months.
Grade 3-5 Worst Degree Toxicity Rate
Adverse events (AEs) were graded per CTCAEv5 and the worst grade experienced per participant was recorded. The Grade 3-5 toxicity rate is defined as the proportion of treated participants whose worst grade AE was Grade 3, 4, or 5 at any point during the observation period, regardless of treatment attribution.
Measured: AEs were recorded from randomisation until 30 days after last chemotherapy dose or 90 days after last durvalumab, ipilimumab, or nivolumab dose, whichever was longer. The treatment duration ranged from 0 to 36 months.
Health-Related Quality of Life (QOL): LC29
EORTC Quality of Life Lung Cancer Module (QLQ-LC29), Importance of QOL issues assessed using a four-point scale (1 = not at all, 4 = very much) and transformed to a 0-100 score, where higher scores mean worse possible symptom burden or severe impact.
Measured: Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50.
Health-Related QOL: EQ-5D-5L
Euro-Quality of Life (EuroQoL) 5 dimension 5 level (EQ-5D-5L) questionnaire, comprising of 5 questions with a score from 1 (no problem) to 5 (extreme problem) and a visual analog scale from 0 (worst) to 100 (best).
Measured: Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start18 Feb 2021
- Primary completion20 Jun 2025
- Study completion30 Jun 2025
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 (3)Papers the sponsor has linked to this study.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- First-line chemotherapy with cisplatin or carboplatin and pemetrexed + durvalumab OR physician's choice of either first-line chemotherapy alone, or ipilimumab and nivolumab.
- Masking
- None (open label)
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- PrECOG, LLC.
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Thoracic Oncology Group Australasia (TOGA), University of Sydney
- Responsible party
- Sponsor
- Investigators
- Patrick Forde, MD, Study chair, Johns Hopkins UniversityAnna Nowak, MD, Study chair, Faculty of Health and Medical Sciences University of Western Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04334759
- Sponsor's protocol ID
- DREAM3R
- Other IDs
- PrE0506, TOGA 18/001, CTC 0231
- Acronym
- DREAM3R
- Status last verified
- Sep 2026
- First submitted
- 2 Apr 2020
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data is proprietary
Publications
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.
PubMed 35078853Kindler 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.
PubMed 34499875Uprety 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.
PubMed 33358660