DREAM3R: A phase 3 trial of durvalumab with chemotherapy as first line treatment in mesothelioma

Abstract

The purpose of this study is to see whether adding durvalumab, a type of immunotherapy, to standard chemotherapy will improve overall survival in patients with pleural mesothelioma (PM).

Who is it for? Participants may be eligible to join this study if they are aged 18 years or above, and have had a diagnosis of PM that cannot be surgically removed.

Study details: The study involves allocating participants to receive treatment with standard chemotherapy given with durvalumab (experimental arm), or physician's choice of: chemotherapy alone OR Ipilimumab and Nivolumab immunotherapy (control arm) . These treatments are allocated by chance. Treatment will be given by infusion until disease worsens or you experience unmanageable side effects.

Study treatment: Chemotherapy and durvalumab (experimental group): This group will receive standard chemotherapy for mesothelioma (cisplatin or carboplatin and pemetrexed) every 3 weeks (one cycle) for a maximum of 6 cycles (about 18 weeks) plus the experimental treatment durvalumab every 3 weeks on the same day as the chemotherapy.

After combination treatment has been completed, participants will continue treatment with durvalumab alone every 4 weeks for as long as they are tolerating the treatment well and the mesothelioma is under control.

Physician's choice of (control group): Chemotherapy alone: This group will receive standard chemotherapy for mesothelioma (cisplatin or carboplatin and pemetrexed) every 3 weeks (one cycle) for a maximum of 6 cycles (about 18 weeks). OR Ipilumumab and Nivolumab immunotherapy: This group will receive Ipilimumab every 6 weeks and Nivolumab every 3 weeks or 2 weeks until disease progression, unacceptable toxicity, or up to 2 years.

After treatment has been completed, participants will receive the same care as they would if they were not on a clinical trial.

After stopping treatment, we would like to follow participants up every 6 weeks for the rest of their life.

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 tumour growth and shrink tumours in some people with cancer. Previous studies of combining durvalumab and chemotherapy showed that this combination is active in advanced mesothelioma.

We plan to enrol 480 participants in this study from hospitals and clinics throughout Australia, New Zealand and the United States of America (USA). Durvalumab is not approved in Australia or any other country for treatment of advanced mesothelioma. Durvalumab is approved for locally advanced lung cancer and advanced bladder cancer in Australia and USA.

It is hoped this research will demonstrate that durvalumab is safe and effective for the treatment of advanced mesothelioma, and that the results of this study will lead to improved outcomes for future mesothelioma patients.