NCT04334759

DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma

DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 214 (actual)
• Sponsor: PrECOG, LLC. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Mesothelioma
• Pleural Mesothelioma
• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
DRUG	Durvalumab	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
DRUG	Standard Chemotherapy	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
DRUG	Ipilimumab and Nivolumab	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

Timeline

• Start date: 2021-02-18
• Primary completion: 2025-06-20
• Completion: 2025-06-30
• First posted: 2020-04-06
• Last updated: 2026-01-22

Locations

57 sites across 3 countries: United States, Australia, New Zealand

Regulatory

• FDA-regulated drug study