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
3524 - Cabazitaxel For Octogenarian Patients With Metastatic Castration-Resistant Prostate Cancer (MCRPC).
Presenter: Paolo Tralongo
Session: Poster Display session 3
Resources:
Abstract
5637 - External Validation of a Prognostic Score in First-Line Metastastic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: David Lorente
Session: Poster Display session 3
Resources:
Abstract
3228 - Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPRI-registry
Presenter: Jessica Notohardjo
Session: Poster Display session 3
Resources:
Abstract
4695 - Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion>5%: a propensity score matching analysis from SEER database
Presenter: Junru Chen
Session: Poster Display session 3
Resources:
Abstract
4438 - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT
Presenter: Morgane Guibert-broudic
Session: Poster Display session 3
Resources:
Abstract
4574 - Safety of new androgen receptor inhibitors (ARi) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a network meta-analysis of randomized controlled trials (RCT)
Presenter: Amelia Altavilla
Session: Poster Display session 3
Resources:
Abstract
3816 - Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry
Presenter: Malou Kuppen
Session: Poster Display session 3
Resources:
Abstract
5180 - A phase 2a study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
1067 - Adding ADT to PSMA-PET/CT-guided SBRT for oligometastatic prostate cancer improves distant progression-free survival
Presenter: Carole Mercier
Session: Poster Display session 3
Resources:
Abstract
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract