Hello, my name is Anna Nowak, and it's a privilege to present this trial in programs. The DREMA clinical trial, developed with chemotherapy as first-line treatment in advanced pleural mesothelioma. This phase three randomized clinical trial is a collaboration between PRECOG, the Thoracic Oncology Group of Australia, and the NHMRC Clinical Trials Group. I'm presenting on behalf of my co-authors, particularly co-PI, Patrick Ford. These are my disclosures. Until recently, standard first-line chemotherapy for malignant pleural mesothelioma was platinum-based doublet with cisplatin or carboplatin with pemetrexid. Recently, the results of the CheckMate 743 clinical trial became available, demonstrating an overall survival benefit for ipilimumab plus nivolumab versus chemotherapy, with a hazard ratio for all patients of 0.74. However, 75% of these patients had epithelioid disease, and this histology seemed to benefit less from this combination, with a hazard ratio of 0.86 that crossed unity, with a majority of the benefit being driven by that in the non-epithelioid population. There are two prior phase two clinical trials, very similar design, the DREAM trial in Australia and the PRIO 505 trial in the USA. And both of these trials met their pre-specified endpoints with promising criteria for activity. Thus, there's still an opportunity to explore first-line treatment for mesothelioma that includes combination chemotherapy and immunotherapy. This is the trial schema. Key eligibility criteria include unresectable malignant pleural mesothelioma with no prior systemic therapy. All participants must have measurable disease by modified resist 1.1 for mesothelioma, and cannot have any prior radiotherapy to measurable disease. ECOG performance status must be 0 to 1. There are a number of stratification factors, including age, sex, histology, epithelioid versus non-epithelioid, and region ANZ versus USA versus other. The trial randomized 480 patients in a two-to-one randomization to the experimental arm comprising development, 1,500 milligrams three-weekly with cisplatin and pemetrexid in standard three-weekly schedule for a maximum of six cycles. And patients in the experimental arm will then continue to have devalamab 1,500 milligrams four-weekly until progressive disease or unacceptable toxicity. The control arm, arm B, patients receive cisplatin or pemetrexid in standard doses for up to six cycles, and then progress to observation. There is an upcoming amendment to incorporate carboplatin area under the curve five as an alternative to cisplatin. And platinum type will also then be a stratification factor. The primary endpoint is overall survival, and secondary endpoints include progression pre-survival, objective tumor response rate by modified resist 1.1 and iRESIST, adverse events, health-related quality of life, and healthcare resource use. There are also important exploratory translational studies looking at potential prognostical predictive biomarkers of tissue and serial blood samples. These, of course, include PD-L1, tumor mutation burden, as well as HLA subtypes, genomic characteristics, and other potential evolving translational studies. Regarding statistical considerations, our 480 patient sample size gives a power of more than 85% if the true overall survival hazard ratio is 0.70 with a two-sided alpha of 0.05. We've assumed a median overall survival chemotherapy alone of 15 months, and for developmental chemotherapy, 21.4 months, with the allowance for crossover, although crossover is not built into the study design. Patients will be recruited over 27 months and followed up for another 24 months. Regarding the study progress, as of early August 2021, there were 24 of 30 sites in Australia and New Zealand activated, and 30 randomized patients. In the USA, 12 of 30 sites have been activated, and 3 of 240 patients have been randomized. In conclusion, this is a large international multicenter randomized clinical trial of immunotherapy and chemotherapy as first-line treatment for malignant thoral mesothelioma. There is a strong biological rationale, and also very sound supporting earlier phase clinical data. We plan to do extensive translational science biospecimen collection in addition to examining quality of life and health economic endpoints. We recognize that the results of checkmate 743 may have a consequence of minimal enrollment of patients with non-epithelioid mesothelioma. Thank you for your attention.

DREMA clinical trial

advanced pleural mesothelioma

chemotherapy

immunotherapy

overall survival