635 A randomised, placebo-controlled, phase I/IIa study evaluating the safety and clinical activity of a novel cancer vaccine (ITOP1) in patients with resectable oesophageal adenocarcinoma (VISTA study)

Abstract

Approximately 10,000 cases of Oesophageal Cancer (OC) are diagnosed across the UK each year, making it the 12^th most common cancer type. Due to its poor prognosis, it is the 6^th most common cause of cancer death with 8,500 attributed deaths annually. Oesophageal adenocarcinoma (OAC) arises from glandular cells predominantly in the lower third of the oesophagus and accounts for three quarters of OC cases in the UK, Europe, and North America. The UK reports the world’s highest rate of OAC, with 7.6 and 1.4 cases per 100,000 age-standardized person-years in men and women, respectively, and demonstrates an association with lower socioeconomic status. Approximately half of OAC patients are diagnosed at Stages 1–3, making curative-intent surgery and neoadjuvant +/- adjuvant chemotherapy the mainstay of treatment. Despite this, around half of patients will experience recurrent disease following surgery, with a median disease-free survival of 11 months. Poor response to neoadjuvant chemotherapy is associated with worse outcomes, highlighting the need for more effective therapies that can be delivered early in treatment. ITOP1 is a proprietary, off-the-shelf, anti-cancer vaccine that is administered intravenously in a homologous prime-boost regimen for the treatment of resectable OAC. To elicit a broad anti-tumour response aiming to prevent disease recurrence, ITOP1 is a multi-epitope vaccine, using cancer antigens identified through mass spectrometry-based, precision immunomics approaches applied to primary OAC samples collected previously (EudraCT:2015-005298-19).

Methods The VISTA study (led by the University of Oxford) is a first-in-human, randomised, placebo-controlled, multi-centre Phase I/IIa study evaluating the safety and clinical activity of ITOP1 administered intravenously to 60 adults with resectable OAC. After enrolment, patients will undergo standard of care neoadjuvant chemotherapy followed by a prime dose of ITOP1 prior to surgery. A boost dose of ITOP1 will be administered following post-surgical convalescence and prior to any adjuvant chemotherapy. The Phase I component of the study will be open-label and single arm, consisting of eight patients. Following a safety assessment, the study will proceed to a 3-to-1 randomised, placebo-controlled Phase IIa component. Tumour and normal tissue will be collected during surgery, alongside paired blood samples. Patients will be followed-up for a minimum of two years in the primary clinical protocol. Key eligibility criteria include HLA matching to ITOP1-delivered epitopes. Primary endpoints are the safety and tolerability of ITOP1. Secondary endpoints are recurrence free survival (RECIST v1.1) and immunogenicity. Enrolment is due to begin in September 2024.