Participant Eligibility
Pre-trial screening
Patients will be eligible for screening for HLA-type testing provided that:
- They give written informed consent to pre-screening
- The Investigator anticipates that they may satisfy the eligibility criteria for entry into the main trial (Phase I or Phase II as applicable at time of screening) detailed below (NB formal screening for the trial should not be performed until the HLA pre-trial screening result is known).
Patients will be eligible for Phase I Safety Lead-in or Phase II screening provided that the following criteria are met in addition to the inclusion and exclusion criteria:
Eligibility criteria for entry into the Phase I Safety Lead-in:
- They give written informed consent to Phase I Safety Lead-in
- They have the relevant HLA type for the Phase I Safety Lead-in treatment: HLA A*02:01
Eligibility criteria for entry into the Phase II screening:
- They give written informed consent to Phase II
- They have the relevant HLA type for the Phase II trial IMP treatment: At least one or more of HLA A*02:01, B*07:02 or B*40:01
Phase I Safety Lead-in & Phase II
Inclusion criteria:
- Histological diagnosis of oesophageal or gastroesophageal junctional (types 1, 2 or 3) adenocarcinoma, deemed suitable for surgery with curative intent
- Deemed suitable for oesophagectomy with curative intent by the relevant multidisciplinary team
- Planned neoadjuvant and adjuvant treatment with FLOT chemotherapy
- ECOG performance status of 0 or 1
- Written informed consent obtained for Phase I Safety Lead-in /Phase II (as applicable).
- Age ≥ 18 years.
- Willing and able to comply with the protocol for the duration of the trial including undergoing treatment, scheduled visits, examinations, biopsies and follow up.
- Adequate normal organ and marrow function as defined below.
|
Lab Test |
Value required |
|
Haemoglobin (Hb) |
≥ 90 g/L |
|
Neutrophil count |
≥ 1.5 x 109/L |
|
Platelet count |
≥ 100 x 109/L |
|
Serum creatinine, or Creatinine Clearance |
≤ 1.5x Institutional Upper Limit of Normal (ULN), or ≥ 40 mL/min (by Cockcroft-Gault formula)
|
|
Aspartate transferase (AST) or Alanine aminotransferase (ALT) |
AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal |
|
Alkaline phosphatase |
≤ 2.5 x ULN |
|
Serum bilirubin |
≤ 1.5 x institutional ULN. This will not apply to subjects with documented Gilbert’s syndrome as evidenced by persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN |
Exclusion criteria:
A patient will not be eligible for the trial if any of the following apply:
- Prior treatment in another clinical trial with an investigational product within 4 weeks prior to Day 1 of the trial; any respective adverse events must have resolved to Grade 1 or lower to be eligible.
- Any contraindications to the FLOT chemotherapy or planned surgery
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with coeliac disease, vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
- Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
- History of allogeneic organ transplant
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s Correction
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with trial requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of severe allergic reactions to any unknown allergens or any components of the trial drugs.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Peripheral sensory neuropathy with functional impairment.
- History of sarcoidosis/sarcoidosis syndrome.
- Major surgical procedure (as defined by the Investigator) within 30 days prior to Day 1 or still recovering from prior surgery.
- SARS-CoV2 vaccine (mRNA, subunit /viral vector or other) within 6 weeks of administration of first dose of trial drug(s); or any live attenuated vaccine within 28 days of first dose of trial drug(s).
- Women who are breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)).
- Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the trial and for 6 months after last dose of trial IMP (both male and female patients). Male participants must use condoms for the duration of the trial and for 6 months after last dose of trial IMP.
- Patients unable to commit to avoiding contact with young children or the severely immunocompromised for 5 days after each IMP dose*
- Any condition that, in the clinical judgment of the treating physician, is likely to interfere with evaluation of trial treatment, interpretation of subject safety or trial results, prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
*Defined as follows:
‘Young Children’ are individuals aged 0 to 12 years’ old whom do not otherwise meet the criteria for ‘severely
immunocompromised’
‘Severely immunocompromised’ are those who meet any of the following criteria:
- Active haematological malignancy (excluding Monoclonal gammopathy of undetermined significance
- (MGUS), or those in currently receiving treatment for a haematological malignancy and/or those within oneyear of bone marrow or stem cell transplant
- Solid organ transplant(s) requiring immunosuppression
- Advanced or untreated HIV/AIDs
- Congenital or primary immunodeficiencies
- Immunosuppressive therapy (equivalent to ≥20 mg/day of prednisone for ≥2 weeks)
- End-stage Renal Disease
- Other condition(s) which, in the opinion of the Principal Investigator, would put close contacts of participants receiving ITOP1 at unreasonable risk should ITOP1 result in clinically significant viral shedding in the 5 days following dosing
Site investigators should discuss with the Chief Investigator any potential patients whose eligibility is affected by this exclusion criterion
