Abstract
TPS640 Background: Pancreatic ductal adenocarcinoma (PDAC) is anticipated to become the second-leading cause of cancer-related deaths by 2030. Systemic therapy remains the mainstay of treatment for those with unresectable/metastatic disease. There is an urgent need for biomarkers to rapidly assess treatment response to spare patients from the significant toxicities and costs of an ineffective regimen, and to guide decision-making for a therapeutic switch with a higher chance of efficacy. Circulating tumor (ct)DNA and PET/MRI represent promising emerging biomarkers for early response prediction. This is a prospective non-randomized study examining the role of ctDNA and PET/MRI in adjudicating early treatment response among patients with unresectable locally advanced or metastatic PDAC receiving systemic therapy. Methods: Approximately 158 patients with advanced PDAC will be recruited at the time of initiation of a new line of treatment in either the first or later-line setting. Patients receiving both standard of care and/or experimental therapies are permitted to enroll. Research blood samples will be collected at pre-treatment, 48 hours, two weeks, one month, and two months after treatment start for analysis of mutant ctDNA (using the FoundationOne/Natera platform). PET/MRI will be performed at pre-treatment and 4 weeks post treatment. All patients must have an ECOG performance status of 0-2 and have radiographically measurable disease. Clinical data will be collected prospectively, including demographics, ECOG performance status, CA 19-9 levels, chemotherapy type and dose intensity, and clinical and radiographic assessment of treatment response using RECIST 1.1 criteria. Enrollment began in August 2021. The primary endpoint is the correlation between change in tumor-derived ctDNA with radiographic progression, as measured by the change in tumor size. The Wilcoxon rank sum test will be used to compare the change in ctDNA with treatment between response vs. resistance. Cox proportional hazard regression modelling will be used to correlate the change in ctDNA with progression-free survival and overall survival. Secondary endpoints include defining thresholds for early chemotherapy switch using dynamic and quantitative changes in ctDNA and PET/MRI biomarkers for use in future prospective trials, establishing the relationship between early changes in PET/MRI and treatment response/resistance, and developing a multivariable model combining ctDNA and PET/MRI biomarkers to predict treatment response/resistance.
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