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DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial
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%. Since 2003, the standard treatment for non-resectable malignant pleural mesothelioma (MPM) has been chemotherapy consisting of pemetrexed and cisplatin (or sometimes carboplatin).
The DREAM3R trial will determine if concurrent chemo-immunotherapy can improve outcomes in newly diagnosed, unresectable MPM. The study builds on signals of effectiveness found in independent single-arm phase II trials that evaluated durvalumab immunotherapy during and after standard chemotherapy. Last May, a report on the PrE0505 trial in the US 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 Jul15). In September 2020, data from the Australian DREAM trial 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 Sep 1).
In both trials, the combination was well-tolerated with no unexpected toxicities.
The DREAM3R trial aims to enroll 480 patients, half in the US and half in Australia/New Zealand. Patients will be randomized 2:1 to receive durvalumab immunotherapy 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 trial will allow both non-epithelioid and epithelioid subtypes. However, study leaders expect that the DREAM3R trial will be a particularly good treatment option for patients with epithelioid subtype MPM, which is associated with significantly better outcomes from chemotherapy than the non-epithelioid subtype. The PrE0505 analyses show a particular benefit in the epithelioid population from the chemo-durvalumab combination. About 75% of all MPM cases are epithelioid subtype.
PrECOG, LLC is sponsoring the DREAM3R study in the US. The University of Sydney, through its NHMRC Clinical Trials Centre, is leading the trial in Australia and New Zealand in collaboration with the Thoracic Oncology Group of Australasia (TOGA). DREAM3R is being conducted with support from Medimmune Ltd and AstraZeneca Pty Ltd, manufacturers of durvalumab.
The lead investigators for the trial are Patrick M. Forde, MD (Johns Hopkins University) in the US and Anna Nowak, MD (The University of Western Australia) in Australia and New Zealand.
Any site that is interested in participating should contact PrECOG.
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 research goals of the ECOG-ACRIN Cancer Research Group. For further information, please visit www.ecog-acrin.org, and follow us on Facebook and Twitter @PrECOGonc and @EAonc.