e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

DuRvalumab with chEmotherapy as first line treAtment in advanced pleural Mesothelioma - A phase 3 Randomised trial. The DREAM3R trial. (#404)

Thomas John 1 , Patrick Forde 2 , Peey Sei Kok 3 , Chris Brown 3 , Zhuoxin Sun 4 , Kenneth O'Byrne 5 , Sonia Yip 3 , Valasamo Anagnostou 6 , Alistair Cook 7 8 , Willem J Lesterhuis 7 , Brett G M Hughes 9 , Lisa Johnson 10 , Martijn Oostendorp 3 , Donna Marinucci 10 , Karen Fitzpatrick 10 , Kate Ford 3 , Nick Pavlakis 11 , Julie Brahmer 2 , Martin R Stockler 3 , Suresh Ramalingam 12 , Anna Nowak 7 8 13
  1. Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
  3. Nhmrc Clinical Trials Centre, University Of Sydney, Camperdown, NSW, Australia
  4. IBCSG Statistical Center, Boston, MA, USA
  5. Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Qld, Australia
  6. Bloomberg-Kimmel Institute for Cancer Immunotherapy, John Hopkins, Baltimore, MD, USA
  7. National Centre for Asbestos Related Diseases, University of Western Australia, Perth, WA, Australia
  8. Medical School, University of Western Australia, Perth, WA, Australia
  9. The Prince Charles Hospital, Cancer Care Services, and University of Queensland, Brisbane, Qld, Australia
  10. PrECOG, Philadelphia, PA, USA
  11. Northern Cancer Institute and University of Sydney, Sydney, NSW, Australia
  12. Winship Cancer Institute, Emory University Hospital, Atlanta, GA, USA
  13. Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia

Objective: Until recently, standard first-line treatment for advanced mesothelioma was platinum chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM and PrE0505) combining durvalumab with platinum-pemetrexed chemotherapy exceeded pre-specified criteria. DREAM3R aims to determine the effectiveness of adding durvalumab to platinum chemotherapy in advanced mesothelioma.

Methods: Treatment naïve patients with advanced mesothelioma will be randomised (2:1) to either (A) durvalumab 1500mg 3-weekly, with chemotherapy (Cisplatin 75mg/m2 or Carboplatin AUC5, and pemetrexed 500mg/m2) 3-weekly for 4-6 cycles, followed by durvalumab 1500mg 4-weekly until disease progression, unacceptable toxicity or patient withdrawal; or (B) chemotherapy alone for 4-6 cycles, followed by observation. Stratification: Age (18-70 years vs. > 70), gender, histology (epithelioid vs. non-epithelioid), platinum drugs (cisplatin vs carboplatin) and region (ANZ vs USA vs others). An amendment is undergoing to add upfront carboplatin AUC 5 as a platinum choice and as a stratification factor.

Key inclusion criteria: MPM of all histologies, measurable disease per modified RECIST 1.1 (mRECIST 1.1) without prior radiotherapy to these sites, ECOG 0-1 and adequate bone marrow, kidney and liver function tests. The primary endpoint is overall survival. Secondary endpoints include progression-free survival; objective tumour response (by mRECIST 1.1 and iRECIST); adverse events; health-related quality of life; and healthcare resource use. Tertiary endpoints: Potential prognostic and/or predictive biomarkers: PD-L1 expression, tumour mutation burden and nuanced genomic characteristics, and HLA type in tissue and serial blood samples; validation of radiological measures of response and studies of possible radiomic biomarkers in mesothelioma. The target sample size is 480 patients recruited over 27 months, with follow up for another 24 months. This provides over 85% power if the true hazard ratio for overall survival was 0.70, with 2-sided alpha of 0.05, and assuming a median survival of 15 months in the control group. ClinicalTrials.gov Identifier: NCT04334759 and ACTRN 12620001199909.