Abstract 5217
Background
Overall survival (OS) of locally advanced esophageal cancer remains poor with a 5-year survival of 15-34%. The standard treatment is definitive radiotherapy delivered with oxaliplatin-based chemotherapy (RCT). Majority of patients (pts) die due to non-complete response, local recurrence and/or metastatic progression and the efficacy of definitive RCT need to be increased. The immune checkpoint inhibitors, anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), demonstrated promising antitumor activity and manageable safety profile when used as monotherapy in metastatic esophageal squamous cell carcinoma. PD-L1 expression increased in esophageal cancer pts after neoadjuvant RCT but still associated with poor OS. The immune tumor microenvironment for tumor response has raised novel hypotheses regarding newer immunomodulatory approaches during radiotherapy, especially abscopal effect to improve local and distant outcome. Durvalumab (MEDI4736) is a selective high affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. We hypothesize that combining durvalumab with RCT can increase local response to treatment and prevent distant metastases.
Trial design
This multicentric, open-label, comparative phase II trial plans to randomize (1:1) 120 pts (≥18 years old, WHO <2, unresectable disease) and evaluates the activity of durvalumab (1500 mg) delivered over 12 months in combination with definitive RCT (IMRT 50 Gy for 5 weeks + FOLFOX4 simplified 1 infusion every 2 weeks during 3 months) compared to definitive RCT alone. Given the lack of safety data from this association, a safety run-in of 6 pts is planned. The main objective is to increase 12-months progression-free survival (PFS) centrally reviewed from 50% to 68% (HR = 0.55). 74 events are necessary to detect this difference with a power of 90% using a one–sided logrank test at 10% level of significance. Main secondary endpoints are safety, PFS and quality of life. Ancillary studies mains to identify biomarkers predicting response to treatment. The first patient will be randomized in May 2019 and 12 sites will recruit pts.
Clinical trial identification
NCT03777813.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer GI tumors.
Funding
AstraZeneca.
Disclosure
L. Quero: Research grant / Funding (institution): AstraZeneca. E.L. Cohen-Jonathan Moyal: Research grant / Funding (institution): AstraZeneca. A. Modesto: Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
5185 - Systemic administration of the hyaluronidase-expressing oncolytic adenovirus VCN-01 in patients with advanced or metastatic pancreatic cancer: first-in-human clinical trial
Presenter: Rocio Garcia-Carbonero
Session: Poster Display session 2
Resources:
Abstract
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract