A Phase II Trial of Neoadjuvant PD-1 Vaccine PD1-Vaxx in Operable MSI High Colorectal Cancer
The aim of Neo-POLEM is to determine the rate of Major Pathological Response (MPR) of \<10% viable tumour cells after administering neoadjuvant PD-1 vaccine IMU-201 (PD1-Vaxx), as measured by percentage change pre- and post-treatment in operable MSI high CRC patients. All patients will be administered three doses of the PD1-Vaxx prior to resection surgery and will be followed up for a minimum of 2 years.
• Patients must have signed and dated a written informed consent form. This must be performed before the performance of any protocol related procedures that are not part of the normal care.
• Patients must be willing and able to comply with the schedule visits, treatment schedules, laboratory tests and other requirements of the study.
• Target Population
• Histologically confirmed adenocarcinoma cancer of the colon and high rectum.
• ECOG Performance status 0 or 1
• Measurable disease per RECIST 1.1 criteria
• Tumour tissue from a colonoscopy must be provided for biomarker analysis. Archival tumour tissue is mandatory for biomarker analysis. If no sample is available, patients will have the option to agree to acquisition of additional tumour tissue during the screening period for future biomarker analyses...
• In order in to be entered into the study, patients must be classified as MSI-High (confirmation of MMR deficiency or MSI-H).
• Stage II (T3-T4 N0) III (any T, N1 or N2, M0) Colorectal cancer
• Radiological evidence of operable CRC, determined by local MDT, usually CT scan.
⁃ Treatment naive patients (no prior anti CRC therapy).
⁃ Screening laboratory values must meet the following criteria
∙ Neutrophils ≥ 1.5x 109/L
‣ Platelets ≥ 100 x 109/L
‣ Haemoglobin ≥ 9.0 g/dl
‣ Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 'CrCl' \> 50 mL/min (using the Cockcroft Gault formula):
⁃ Female CrCl = (140 - age in years) x weight (kg) x 1.04 serum creatinine (µmol/l)
• Male CrCl = (140 - age in years) x weight (kg) x 1.23 serum creatinine in µmol
‣ Total bilirubin ≤ 1.5 x ULN; for patients with documented/suspected Gilbert's disease, bilirubin ≤3 x ULN
‣ AST ≤1.5 x ULN
‣ ALT ≤1.5 x ULN
⁃ Age and Reproductive Status
⁃ Age ≥ 18 years
⁃ Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug.
⁃ Women must not be breastfeeding.
⁃ Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception, as indicated in the informed consent form. Contraception must be used for the duration of treatment and for a period of 180 days after last dose of study drug.
⁃ Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception, as indicated in the informed consent form for a period of 180 days. Men who are sexually active with WOCBP must continue contraception for 180 days after the last dose of investigational drug (combination or monotherapy). In addition, male patients must be willing to refrain from sperm donation during this time.
⁃ Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.