Abstract 5938
Background
Oesophageal cancer is the 6th most common cause of cancer death with incidence of adenocarcinomas (EAC) increasing in western countries. Long term survival is poor (<5%) (ESMO guidelines 2016) and mutational signatures of EAC suggest patients with "mutagenic" or "DDR" signatures can benefit from immune-checkpoint blockers (ICB) (Secriert et al. Nat gen 2016). However, there is uncertainty around the population to benefit from ICBs. Circulating tumour DNA (ctDNA) can be used to predict responses to immuno-oncology (IO) agents (Howell J, Trans res 2017). TP53 mutations is frequent in EAC 6 and ctDNA-TP53 mutations can be measured/followed in plasma to track tumour behaviour (response, clonal changes) during treatment (Zill O. Clin Can Res 2018, Fisher O. Gut 2017). Next-generation sequencing (NGS) provides high sensitivity, coverage and the possibility to interrogate tumour treatment-response and heterogeneity.
Trial design
CALIBRATION is a single-centre, open-label, pilot trial of durvalumab (1500mg/4w) for patients with EAC progressing to standard chemotherapy. Pts with measurable disease undergo biopsies at screening/C3/progression alongside weekly blood sampling. Primary objective: asses if early changes in TP53 ctDNA variant allele fraction (VAF) levels, by weeks 4 and/ or 7 can predict durable (6 month) RECIST V 1.1 responses (Complete or Partial Response, Stable Disease). We plan to recruit 19 pts with a 5 % significance (one-sided) and 80 % power to detect if ctDNA changes correctly predict radiological response in ≥ 70 % pts. The trial opened to recruitment in October 2018, 13 pts have been pre-screened and 4 pts included. An interim analysis is planned for September 2019. Secondary endpoints include characterization of paired blood/biopsy samples from pts pre/post durvalumab of: • genomic heterogeneity (evolution of mutational signatures under IO) and changes in the tumour microenvironment (dynamics of T-cell populations). • changes in ctDNA and PBMC markers to identify biomarkers of resistance/response. • predictive value of the mutagenic and DDR signatures to predict response to IO compounds.
Clinical trial identification
NCT03653052.
Editorial acknowledgement
Legal entity responsible for the study
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge.
Funding
AstraZeneca.
Disclosure
S. Dovedi: Leadership role: AstraZeneca.
Resources from the same session
2152 - Inferring the correlation between incidence rates of melanoma and the average tumor-specific epitope binding ability of HLA class I molecules in different populations
Presenter: Istvan Miklos
Session: Poster Display session 3
Resources:
Abstract
4382 - Thermal Liquid Biopsy as a Valuable Tool in Lung Cancer Screening Programs
Presenter: Alberto Rodrigo
Session: Poster Display session 3
Resources:
Abstract
2465 - Towards a screening test for cancer by circulating DNA analysis
Presenter: Rita Tanos
Session: Poster Display session 3
Resources:
Abstract
3788 - Evaluation of a successful launch of the MammaPrint and BluePrint NGS kit
Presenter: Leonie Delahaye
Session: Poster Display session 3
Resources:
Abstract
3863 - Analysis of prognostic factors on overall survival in elderly women treated for early breast cancer using data mining and machine learning
Presenter: Pierre Heudel
Session: Poster Display session 3
Resources:
Abstract
1993 - Circulating tumor cell detection in epithelial ovarian cancer using dual-component antibodies targeting EpCAM and FRα
Presenter: Na Li
Session: Poster Display session 3
Resources:
Abstract
4281 - CEUS of the breast: Is it feasible in improved performance of BI-RADS evaluation of critical breast lesions?——A multi-center prospective study in China
Presenter: Jun Luo
Session: Poster Display session 3
Resources:
Abstract
2268 - Classification of abnormal findings on ring-type dedicated breast PET for detecting breast cancer
Presenter: Shinsuke Sasada
Session: Poster Display session 3
Resources:
Abstract
4035 - Prediction of benign and malignant breast masses using digital mammograms texture features
Presenter: Cui Yanhua
Session: Poster Display session 3
Resources:
Abstract
5678 - Nanomaterials Augmented LDI-TOF-MS for Hepatocellular Carcinoma Diagnosis and Classification
Presenter: Jian Zhou
Session: Poster Display session 3
Resources:
Abstract