1940P CALIBRATION: Can early changes in circulating tumour DNA (ctDNA) predict durable tumour responses in patients (pts) with advanced esophageal adenocarcinoma (EAC) receiving anti PD-L1 antibody durvalumab (D)?
Annals of Oncology(2020)
摘要
Response of EAC to immune-checkpoint blockade (ICB) is modest and clinicians lack biomarkers for pt selection. EAC's mutational signature profile suggest 'mutagenic' & 'DDR' subtypes might respond to ICB. Furthermore, ctDNA can detect treatment & genomic variations before other tests. Prospective, open-label, pilot trial of D (1500mg/4wk) for advanced EAC. Intensive blood sampling (PBMCs, plasma) & tumor biopsies are taken at pre-defined time-points (screening/wk12/disease progression). Tumour-derived variant allele fractions (VAF) & copy-number alterations (CN) are analyzed using Guardant360 assay. Primary objective: determine if early changes (wk4/7) in ctDNA (VAF, CN) correlates with long-term radiological responses (wk26). Enrolment of 19 evaluable pts is planned. Translational studies will analyze D on the immuno-genomic landscape of EAC. We report the interim data. 7 pts were recruited (all male, median age: 71.7 yr, 1 patient HER2+), 6 received D. Prior chemotherapy: perioperative only in 2/6, ≥ 1 line in 4/6. Three pts received ≥ 3 doses of D. Adverse events (AE): 68% Grade 1-2, 32% (8/25) Grade 3 (none drug-related). Two drug-related AE (hyperamylasemia, hypothyroidism) led to dose delay and withdrawal, respectively. Both resolved. Primary endpoint: 'changes in “total-ctDNA fraction" and RECIST1.1 response' were evaluable in 4/6 pts:Table: 1940PPtRelative change in total ctDNA fraction (scr to wk 7)Response11.85PD22PD30.31Partial response (PR)41.07Stable Disease Open table in a new tab . Also, individual gene changes reflect RECIST responses: -Pt3 had PR & ≥10% relative reduction in VAFs (PI3KCA, TP53, APC, ERBB2) & CNs (CDK4, FGFR2, CCNE1). -Pt2 had PD & ≥10% relative increase of VAFs (TP53, BRCA1, ATM) & CN (KRAS, EGRF). D was well tolerated with potential activity in EAC. Data suggest a relationship between changes in ctDNA & RECIST response. Mature data is required. Recruitment & translational studies are ongoing, mutational signature profile (WGS data) of 4pts will be presented.
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关键词
tumour dna,ctdna,advanced esophageal adenocarcinoma,durable tumour responses
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