Tremelimumab and Durvalumab in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery

Inclusion Criteria

• Patients must have histologically or cytologically confirmed colorectal cancer with liver metastases deemed resectable by a general or liver surgeon (resectability may involve the use of ablative techniques to some but not all liver metastases); those patients with known disease outside of the liver are not eligible (except for patients with primary lesions in place that are planned for resection or nonspecific lung metastases = 10 mm with spiral computed tomography (CT) scan
• All lines of prior therapy accepted; subjects with prior hepatic or extra-hepatic resections of metastatic disease will be included
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status = = 70%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin = 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Known or ordered molecular testing for MSI, BRAF, and KRAS status
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:
• Women = 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
• Ability to understand and the willingness to sign a written informed consent document
• Weight > 30 kg (required for flat dose-based administration of study agents)

Exclusion Criteria

• Prior chemotherapy 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Prior exposure to T cell checkpoint inhibitor therapies, including durvalumab and tremelimumab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• History of active primary immunodeficiency
• Women who are pregnant, which includes women with a positive pregnancy test at enrollment or prior to the administration of study medication, or breastfeeding are not allowed on study
• Receipt of a live vaccine within 30 days of study entry
• Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: a) patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician; b) patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician
• Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment, concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Major surgical procedure within 28 days prior to the first dose of IP; Note: local surgery of isolated lesions for palliative intent is acceptable
• History of allogenic organ transplantation
• Known active infection including tuberculosis (cli