2019 ASCO Annual Meeting!
Session: Genitourinary (Nonprostate) Cancer
Type: Poster Session
Time: Monday June 3, 1:15 PM to 4:15 PM
Location: Hall A
Correlation of circulating tumor DNA (ctDNA), tissue-based genomic profiling and clinical efficacy in the biomarker directed Ph1b trial in metastatic bladder cancer (BISCAY).
Genitourinary (Nonprostate) Cancer
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #379)
J Clin Oncol 37, 2019 (suppl; abstr 4553)
Author(s): Danielle Carroll, Rob McEwen, Iwanka Kozarewa, Elizabeth Harrington, Anne L'Hernault, Jayantha Ratnayake, Richard Mather, Darren Hodgson, J Carl Barrett, Jan G. C. E. Cosaert, Pierre Emmanuel Brachet, Petros Grivas, Simon Chowdhury, Thomas Powles, Donal Landers; Translational Science, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom; AstraZeneca, Cambridge, United Kingdom; Oncology Translational Science, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom; Astrazeneca, Cambridge, United Kingdom; AstraZeneca, Royston, United Kingdom; AstraZeneca, Boston, MA; Translational Sciences, IMED Biotech Unit, AstraZeneca, Waltham, MA; AstraZeneca, Cambridge, NJ, United Kingdom; GINECO-Centre François Baclesse, Caen, France; University of Washington, School of Medicine, Seattle, WA; Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute, London, United Kingdom; Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust, London, United Kingdom; AstraZeneca, Macclesfield, United Kingdom
Background: BISCAY is a biomarker-directed Ph1b multi-arm platform study exploring the combination of targeted therapies with anti-PD-L1, Durvalumab, in advanced urothelial cancer. Methods: Next generation sequencing (NGS) of tumour tissue samples from > 380 patients(pts) was performed using the FoundationOne assay alongside IHC for PD-L1. ct DNA from pts enrolled in trial modules at treatment initiation was profiled using the Guardant Health OMNI platform assessing a panel of 500 genes. For a subset of pts, serial plasma samples were also analysed to monitor early signs of response vs. resistance and changes in ct DNA dynamics using a bespoke NGS panel of 10 genes. Results: To date 149 pts have been actively enrolled across 7 different biomarker selected and unselected treatment modules. Across all screened pts the most prevalent genomic alterations in tumour tissue were TERT promoter (65%), TP53 (59%), KMT2D 21%, KDM6A 21%, with the most common CNV CDKN2A/B loss (32 %). All enrolled pts tested had detectable ctDNA in plasma. Similar genomic alterations, both frequency and type, were detected in both plasma ctDNA and tumour tissue with high concordance for module specific biomarkers used for patient allocation (80% (8/10) for ATM, BRCA1 and 2). Alterations in putative biomarkers predictive of response to anti-PD-L1, such as HRR/MMR alterations and high bTMB levels ( > 20mut/Mb) were observed in22% and 40% patient plasma samples, respectively. Correlations between biomarkers across modules treatment efficacy have been explored. Conclusions: All pts with advanced bladder cancer enrolled on BISCAY who were plasma profiled had detectable ctDNA; frequencies of genomic alterations (in both tumour tissue and plasma) were comparable to prior published data sets. ctDNA may be an attractive alternative to tissue-based NGS, providing comprehensive dynamic snapshots of genomic landscapes at the start and during therapy, and warrants further prospective investigation in trials.
1. CALGB 90601 (Alliance): Randomized, double-blind, placebo-controlled phase III trial comparing gemcitabine and cisplatin with bevacizumab or placebo in patients with metastatic urothelial carcinoma.