KRAS Peptide Vaccine, Nivolumab, and Ipilimumab for the Treatment of Resected Pancreatic Cancer or MSS Colorectal Cancer

Inclusion Criteria

• Age >= 18 years
• Have histologically- or cytologically-proven adenocarcinoma of the pancreas (PDAC) or MSS colorectal (CRC) in one of the following categories: * PDAC must have no evidence of disease and last dose of neoadjuvant and/or adjuvant chemotherapy/radiation therapy/or surgery must be < 6 months from study entry * Metastatic MSS CRC after progression on 2 more lines of chemotherapy in the metastatic setting including 5-flurouracil, irinotecan, and oxaliplatin exposure. Patients treated with FOLFOXIRI may enroll after progression or intolerance to that regimen
• For metastatic MSS CRC cohort, must have tumor lesions amenable to repeated biopsy, and patient’s acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the principal investigator)
• For metastatic MSS CRC patients, must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping
• Have one of the six KRAS mutations (KRAS^G12C, KRAS^G12V, KRAS^G12D, KRAS^G12A, KRAS^G13D or KRAS^G12R) expressed in tumor
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy greater than 6 months
• Leukocytes >= 3,000/mcL
• Lymphocytes > 500/mm^3
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100 x 10^3/uL
• Hemoglobin >= 9.0 g/dL
• Total bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
• Alkaline phosphatase =< 5.0 x ULN
• Creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula)
• Albumin >= 3.2 g/dL
• Lactate dehydrogenase (LDH) =< 1.5 x ULN
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]). NOTE: If a patient has a positive or indeterminate serum or urine pregnancy test, then an ultrasound must be done to rule out pregnancy to enroll on trial * WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 4 weeks (duration of ovulatory cycle) for a total of 5 months post treatment completion * Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion * At least one barrier method of contraception must be employed by all sexually active patients (male and female), regardless of other methods, to prevent the transfer of body fluids
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study
• Any of the following procedures or medications: * Within 2 weeks prior to initiation of study treatment: ** Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses =< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease ** Palliative or adjuvant radiation or gamma knife radiosurgery ** Chemotherapy * Within 4 weeks prior to initiation of study treatment: ** Any investigational cytotoxic drug. Exposure to any non-cytotoxic drug within 4 weeks or 5 half-lives (whichever is shorter) is prohibited. If 5 half-lives is shorter than 4 weeks, agreement with investigational new drug (IND) sponsor is mandatory ** Any investigational device ** Non-oncology vaccines containing live virus. Examples include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine ** Allergen hyposensitization therapy ** Growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin ** Major surgery (excludes celiac plexus block, biliary stent placement, and other minor procedures such as dental work, skin biopsy, etc.)
• Patients with a history of prior treatment with immunotherapy agents (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, antiCD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies)
• History of severe hypersensitivity reaction to any monoclonal antibodies or related compounds or to any of their components (e.g., history of severe hypersensitivity reactions to drugs formulated with polysorbate 80)
• Patient has a known history or evidence of brain metastases
• Has an active known or suspected autoimmune disease or which has required systemic therapy in the last 2 years. Subjects 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
• Known history of interstitial lung disease or of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has a pulse oximetry < 92% on room air
• Requires the use of home oxygen
• Has a known history of human immunodeficiency virus (HIV) (HIV1/2 antibodies), hepatitis B, or hepatitis C infection
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have been diagnosed with another cancer or myeloproliferative disorder in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, or a low grade prostate cancer not requiring therapy
• Has a diagnosis of immunodeficiency
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded
• Any other sound medical, psychiatric, and/or social reason as determined by the investigator
• Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements
• Patient is unwilling or unable to follow the study schedule for any reason
• Patient is pregnant or breastfeeding
• For metastatic MSS CRC cohort, any peritoneal involvement by the tumor
• For metastatic MSS CRC cohort, any radiological or clinical pleural effusions or ascites
• For metastatic MSS CRC cohort, patients on parenteral nutrition
• For metastatic CRC cohort, patients with any single liver metastases greater than 5 cm or greater > 50% liver involvement
• For metastatic MSS CRC cohort, history of malignant bowel obstruction