The DREAM3R phase three clinical trial is now enrolling patients with newly diagnosed unresectable malignant pleural mesothelioma (MPM) throughout the US, Australia, and New Zealand. The DREAM3R study builds on signals of effectiveness found in independent single-arm phase two trials, PrE0505 and DREAM. These trials evaluated durvalumab immunotherapy during and after standard chemotherapy.
"DREAM3R will determine if concurrent chemo-immunotherapy can improve outcomes in malignant pleural mesothelioma, especially for the majority of patients with the epithelioid subtype," said lead US investigator Patrick Forde, MD, of Johns Hopkins University. "Both the DREAM and PrE0505 phase 2 trials showed remarkable results in MPM with the combination of chemotherapy and durvalumab, and warrant confirmation in a randomized phase 3 trial."
The PrECOG, LLC cancer research group is sponsoring the study in the US. The University of Sydney, through its NHMRC Clinical Trials Group, is leading the trial in Australia and New Zealand in collaboration with the Thoracic Oncology Group of Australasia (TOGA). The lead investigator for the trial in Australia and New Zealand is Anna K. Nowak, PhD, FRACP (The University of Western Australia). DREAM3R is being conducted with support from Medimmune Ltd and AstraZeneca Pty Ltd, manufacturers of durvalumab.
"It is a privilege for PrECOG to conduct this important trial, the results of which could change the standard of care for patients with malignant pleural mesothelioma," said Peter J. O'Dwyer, MD, CEO and chair of PrECOG, LLC.
Pleural mesothelioma is a rare and aggressive form of cancer with a poor prognosis and limited treatment options. Historically, the five-year survival rate is less than 10%. The pleura is a thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity. Since 2003, the standard treatment for non-resectable malignant pleural mesothelioma has been chemotherapy consisting of pemetrexed and cisplatin (or sometimes carboplatin).
PrE0505: In May 2020, a report on the PrE0505 trial in the US (n=55 patients) showed that the study met its primary endpoint with a median overall survival (OS) of 20.4 months (one-sided P=0.0014) as compared to the historical control of 12.1 months (Vogelzang NJ J Clin Oncol 2003). OS rates at 12 and 24 months were 70.4% and 44.2%, respectively.
DREAM: In September 2020, data from the DREAM trial by the Australian trial groups showed that the study met its primary endpoint of progression-free survival, with 31 (57%; 95% CI 44-70) of 54 patients alive and progression-free at six months. (Nowak AK Lancet Oncol 2020).
In both trials, the combination was well-tolerated by patients, with no unexpected toxicities.
"We expect that the DREAM3R trial will be a particularly good treatment option for the 75% of MPM patients with epithelioid subtype, which is associated with significantly better outcomes from chemotherapy than the non-epithelioid subtype," said Dr. Forde. "Also, in our analyses of PrE0505, we have seen a particular benefit in the epithelioid population from the chemo-durvalumab combination."
The DREAM3R trial aims to enroll 480 men and women between 18 and 70 years of age with malignant pleural mesothelioma that cannot be removed by surgery. It will enroll patients with both non-epithelioid and epithelioid subtypes. Patients will be randomized 2:1 to receive durvalumab plus four to six cycles of chemotherapy (pemetrexed/cisplatin) or chemotherapy alone. Patients in the experimental group will continue on maintenance durvalumab following chemotherapy until disease progression, unacceptable toxicity, or patient withdrawal.
The official study title is DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial.
The trial ID is PrE0506. Find the trial on ClinicalTrials.gov by its record number, NCT04334759.
Durvalumab is an antibody (a type of human protein) that works by blocking a substance called Programmed Death-Ligand 1 (PD-L1) on tumor cells. 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. Durvalumab is FDA approved in some cancers (lung and bladder), but it remains experimental in mesothelioma.
PrECOG, LLC is a cancer research group formed as a not-for-profit limited liability company in 2006 by the ECOG Research and Education Foundation, Inc. It operates outside of the National Cancer Institute's federal funding structure, known as the National Clinical Trials Network. A central focus of PrECOG is to support the overall scientific mission and research goals of the ECOG-ACRIN Cancer Research Group. For more information, please visit http://www.ecog-acrin.org, and follow us on Facebook and Twitter @PrECOGonc and @EAonc.