Nivolumab and Chemotherapy with or without CV301 Vaccine in Treating Patients with Resectable Hepatic-Limited Metastatic Colorectal Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 and/or sufficient to undergo both perioperative systemic chemotherapy and hepatic surgery as determined by surgical and medical oncology evaluations
• Histologically confirmed hepatic-limited metastatic colorectal cancer
• Genomic testing results are required. FoundationOne platform is preferred, however results from an equivalent genomic platform may be used after discussion with the sponsor investigator
• Completely resectable disease as determined by the guidelines below and surgical oncology evaluation. Patients with bilobar disease that requires resection and ablation are allowed provided the surgical oncologist can render the patient NED (no evidence of disease) at the conclusion of the operation. Synchronous primary colorectal and metastatic hepatic tumors are eligible, provided all disease can be resected in a single operation. NOTE: Subjects who had surgery for their primary tumor prior to registration to this trial are still eligible. Additionally: * No radiographic evidence of involvement of: extrahepatic bile ducts, main portal vein or celiac/retroperitoneal lymph nodes * Adequate predicted functional liver remnant (FLR) as measured by computed tomography (CT) and 3-dimensional (3D) CT volumetry as deemed by the individual site surgical oncologists
• Patients must be treatment naive with respect to their stage IV colorectal cancer. History of prior adjuvant systemic chemotherapy containing oxaliplatin is allowed as long as as it has been greater than 12 months from completion of oxaliplatin to study enrollment. NOTE: Neoadjuvant pelvic chemoradiotherapy as part of the management of synchronous metastatic rectal cancer is allowed, provided chemoradiation was completed prior to enrollment on study
• Platelet count >= 100,000 mm^3 (within 28 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500 u/L (within 28 days prior to registration)
• Hemoglobin (Hgb) >= 9 g/dL (within 28 days prior to registration)
• Creatinine < 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 60 mL/min for participants with creatinine levels > 1.5 x ULN (within 28 days prior to registration) * Cockcroft-Gault formula will be used to calculate creatinine clearance
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to registration) * If patient has conditions of congenital hyperbilirubinemia, then patient must have isolated hyperbilirubinemia (e.g. no other liver function test abnormalities) with maximum bilirubin < 2 x institutional ULN
• Aspartate aminotransferase (AST) =< 5 x ULN; given presence of liver metastases (within 28 days prior to registration)
• Alanine aminotransferase (ALT) =< 5 x ULN; given presence of liver metastases (within 28 days prior to registration)
• Alkaline phosphatase < 2.5 x ULN (within 28 days prior to registration)
• International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy, in which case they must be on a stable dose (within 28 days prior to registration)
• Females of childbearing potential must have a negative serum pregnancy test within 24 hours of study drug. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months without another cause, or a documented serum follicle stimulating hormone (FSH) >= 35 mIU/mL. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Females of childbearing potential (FOCBP) and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 5 months (FOCBP) and 7 months (males) after discontinuation of nivolumab. For subjects in the vaccination Arm, if the vaccination is the last study drug administered the timeframe for contraception is 4 months from last dose of vaccination. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria

• Patients with mutations in or deficient expression of one or more of the mismatch repair genes listed: MSH2, MSH3, MSH6, MLH1, PMS1, PMS2
• Active infection requiring systemic therapy
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Second primary malignancy within the last 2 years. Clear exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 2 years or is considered likely to be cured by their oncologist if the period has been less than 2 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix, basal or squamous cell skin cancer, and superficial bladder cancer). Patients with chronic lymphocytic leukemia will be allowed if their blood counts are within acceptable hematologic parameters and if they are not currently requiring cytotoxic or biologic anticancer treatment (supportive treatment such as intravenous immunoglobulin [IVIG] is permitted).
• Metastatic disease not limited to the liver
• Disease not amenable to complete resection, not resectable within the confines of a single surgery, or where resection would result in inadequate functional liver remnant
• Has a known history of immunodeficiency including but not limited to patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and chronic hepatitis B/C. Testing is not required.
• Patient with clinically significant cardiomyopathy, coronary disease, heart failure New York Heart Association (NYHA) class III or IV, or cerebrovascular accident (CVA) within 1 year of study enrollment (CV301)
• Subjects with known severe allergy to eggs, egg products, or aminoglycoside antibiotics (for example, gentamicin or tobramycin) (CV301)
• Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Participants with history of life-threatening toxicity related to prior immune therapy (e.g. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (e.g. Hormone replacement after adrenal crisis)
• Patients with serious or uncontrolled medical disorders.
• Treatment with botanical preparations (e.g. herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment.
• History of allergy or hypersensitivity to study drug components.
• Has received a live vaccine within 30 days of the planned start of study therapy. Note: seasonal flu vaccines for injection are generally inactivated vaccines and are allowed, however intranasal influenza vaccines are live attenuated vaccines and are not allowed.
• History of allogeneic stem cell or solid organ transplant