The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted Clinical Trial Application (CTA) approval for Infinitopes Ltd's novel cancer vaccine ITOP1, marking a significant advancement in immunotherapy for oesophageal cancer. The first-in-human Phase I/IIa clinical trial will evaluate this precision 'off-the-shelf' vaccine designed to prevent recurrence in patients with surgically resectable oesophageal adenocarcinoma (OAC).
ITOP1 represents a potentially groundbreaking approach to cancer immunotherapy, targeting specific tumor antigens to stimulate robust immune responses against residual cancer cells following surgery. The vaccine aims to address the high recurrence rates in OAC, a disease with particularly poor survival outcomes.
Innovative Mechanism and Trial Design
ITOP1 works by activating CD8+ cytotoxic T cells to eliminate cancer cells expressing specific target antigens, thereby reducing the risk of disease recurrence. These targets were identified using Infinitopes' proprietary Precision Immunomics™ platform, which employs AI/ML-driven immunopeptidomics to discover tumor antigens with high specificity and conservation across patients.
The VISTA study (Vaccination with ITOP1 in resectable oesophageal adenocarcinoma, to evaluate Safety, Tolerability & Anti-tumour activity) is designed as a double-blind, randomized, placebo-controlled trial involving 60 patients. The trial will assess ITOP1's safety profile and efficacy in reducing OAC recurrence rates.
"Half of us will suffer cancer in our lifetimes, so we need better, affordable treatments for the disease," said Prof Mark Middleton, Chief Investigator, Head of Oncology & Co-director at CRUK Oxford Centre, University of Oxford. "ITOP1 is an exciting new immunotherapy with the potential to make a difference across a wide range of cancers, bringing hope to many patients."
What distinguishes this trial is its innovative timing of vaccine administration. Patients will receive ITOP1 in a prime/boost regimen alongside standard care, with a priming dose following neoadjuvant therapy and a boost dose before adjuvant FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy. Notably, the VISTA trial will be among the first globally to administer a cancer vaccine in the neoadjuvant setting while the primary tumor remains in place, potentially enhancing protection through epitope spreading.
Addressing a Significant Unmet Need
Oesophageal cancer represents a substantial health burden in the UK, with approximately 10,000 new diagnoses and 8,500 deaths annually. It ranks as the sixth leading cause of cancer deaths in the country, with only 20% of patients surviving beyond five years. The disease is particularly challenging due to late diagnosis resulting from limited early symptoms and the absence of effective population screening.
Dr. Jonathan Kwok, Chief Executive Officer & Co-Founder at Infinitopes, highlighted the rapid development timeline: "We are delighted that we have advanced our lead vaccine candidate, ITOP1, from university research to a groundbreaking clinical programme in just over three years. This marks a major performance milestone for the company, bringing Infinitopes an important step closer to offering lifesaving solutions for patients with oesophageal and other aggressive cancers."
Trial Implementation and Future Outlook
The multicentre VISTA study will be conducted at four specialist cancer centres across the UK under Prof Middleton's leadership. The trial is scheduled to commence in Q2 2025, with details available in the UK Clinical Trials Registry under Integrated Research Application System (IRAS) project 1008088.
Infinitopes has recently strengthened its scientific and clinical team with key industry appointments, including Dan Menichella and Jo Brewer, PhD, to support ITOP1's clinical development. The company has secured nearly $20 million in funding from various investors, including Cancer Research Horizons and the Cancer Research Institute.
"Infinitopes' Precision Immunomics approach has the potential to revolutionise cancer treatment as we know it today," said Dan Menichella, Non-Executive Director at Infinitopes. "I am very excited for the start of our VISTA study, to validate our ITOP1 vaccine and the fundamental enabling technologies."
The technology behind ITOP1 may have broader applications beyond oesophageal cancer. The high tumor-specificity and inter-patient conservation of the targeted antigens suggest potential clinical applicability across multiple cancer types, potentially opening new treatment avenues for various solid tumors.
If successful, this novel approach could significantly improve the standard of care for OAC patients by reducing metastases and cancer-related deaths, while establishing a new paradigm for cancer vaccine development and implementation.
