| Eligibility |
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
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