Study of an Individualized Vaccine Targeting Neoantigens in Combination With Immune Checkpoint Blockade for Patients With Colon Cancer

Inclusion Criteria

For Vaccine Production Stage:

Patients with a high-risk stage II or stage III colon cancer, including high-risk stage II colon cancer defined as meeting any of the following criteria: T4 tumors, Grade ≥3, clinical presentation with bowel obstruction or perforation, histological signs of vascular or lymphatic or perineural invasions, and <12 nodes examined
Patient has evidence of minimal residual disease (MRD) prior to initiating adjuvant chemotherapy (ACT) based on the presence of ctDNA
Patient has received approximately <6 weeks of ACT.
Margin negative (R0) pathology on resection
Availability of formalin fixed, paraffin embedded (FFPE) tumor specimens
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 or equivalent for patients 12 to 17 years of age
Patient has adequate organ function as defined by: peripheral white blood cell (WBC) count ≥3000/mm^3, absolute lymphocyte count (ALC) ≥800/mm^3, absolute neutrophils count (ANC) ≥1500/mm^3, platelets ≥100,000/mm^3, hemoglobin ≥9 g/dL, albumin ≥3 g/dL, calculated creatinine clearance >50 mL/min using Cockcroft-Gault equation, alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN), total serum bilirubin ≤1.5 × ULN OR direct bilirubin ≤1 × ULN, international normalized ratio (INR), prothrombin time (PT), or partial thromboplastin time (PTT) ≤1.5 × ULN, unless patient is receiving anti-coagulant therapy, in which case patients are eligible if PT and PTT are within therapeutic range of intended use of anti-coagulants, and carcinoembryonic antigen levels ≤1.5 × ULN.
A woman of childbearing potential (WCBP) must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment

For Study Treatment Stage:

Have a confirmed diagnosis of high-risk stage II or stage III micro-satellite stable (MSS)-colon cancer and have had their tumor surgically resected, have completed standard ACT and have no evidence of disease radiographically, and have evidence of MRD based on detection of ctDNA following ACT
ECOG performance status of 0 to 1 or equivalent for patients 12-17 years of age
Have adequate organ function with peripheral WBC count ≥2000/mm^3, ALC ≥500/mm^3, ANC ≥1000/mm^3, platelets ≥75,000/mm^3, hemoglobin ≥9 g/dL, albumin ≥3 g/dL, calculated creatinine clearance >40 mL/min using Cockcroft-Gault equation, ALT and AST ≤3 × ULN, total serum bilirubin ≤1.5 × ULN OR direct bilirubin ≤1 × ULN, and INR, PT, or PTT ≤1.5 × ULN
If a WCBP, must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment
If male and sexually active with a WCBP, must agree to use highly effective contraception such as latex condom plus partner use of a highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment.

Exclusion Criteria

For Vaccine Production Stage:

Patients with micro-satellite instable (MSI)-high disease
Patients with known tumor mutational burden (TMB) <1 non-synonymous mutations/megabase
Patients with known DNA Polymerase Epsilon mutations
Known exposure to chimpanzee adenovirus (ChAd) within the prior 6 months, plan to receive a ChAd-based vaccine in the next 6 months, and/or any history or anaphylaxis in reaction to a vaccination
Bleeding disorder or history of significant bruising or bleeding following intramuscular (IM) injections or blood draws
Immunosuppression anticipated at time of study treatment
Patient has received prior therapy consisting of anti-cytotoxic T lymphocyte-associated antigen (CTLA-4), anti-programmed cell death-1 receptor (PD-1), anti-programmed death ligand-1(PD-L1), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
History of allogeneic tissue/solid organ transplant
Active or history of autoimmune disease or immune deficiency
History of other cancer within 2 years
Active tuberculosis or recent (<2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C or known history of positive test for human immunodeficiency virus (HIV) if CD4+ T-cell count is ≤200 cells/microliter.
History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis)
Myocardial infarction within 3 months or prior to study treatment, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure (New York Heart Association [NYHA] Grade 3 and 4)
Pregnant, planning to become pregnant, or nursing

For Study Treatment Stage

Patient is receiving treatment with investigational products and/or other anti-cancer therapies.
Known exposure to ChAd within the prior 6 months, plan to receive a ChAd-based vaccine in the next 6 months, and/or any history or anaphylaxis in reaction to a vaccination
Immunosuppression from concurrent, recent (≤4 weeks) or anticipated treatment with systemic corticosteroids or other immunosuppressive medications or conditions such as hypogammaglobulinemia, or radiation exposure
Patients who have not recovered from prior cancer therapy-induced AEs
Any severe concurrent non-cancer disease
Active tuberculosis or recent (<2 weeks) clinically significant infection, evidence of active hepatitis B or hepatitis C, or known history of positive test for HIV if CD4+ T-cell count is ≤200 cells/microliter
History of pneumonitis requiring systemic steroids for treatment
Myocardial infarction within 6 months prior to initiating study treatment, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure (NYHA Grade 3 and 4).
Pregnant, planning to become pregnant, or nursing