Phase I Study of Dual Immune Checkpoint Blockade (Anti-PD-L1 (Durvalumab) (MEDI4736) and Anti-CTLA4 (Tremelimumab) Plus Yttrium-90 (Y-90) Radioembolization & Stereotactic Body Radiation Therapy (SBRT) in Refractory Metastatic MSS (Microsatellite Stable) Colorectal Cancer With Liver Metastases

• Histologic or cytologic confirmation of metastatic microsatellite stable colorectal cancer

• Liver metastases not amenable to resection for which palliative Y-90 and SBRT is considered appropriate standard therapy

• Patients should have received at least one prior standard therapy for metastatic disease. Prior therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine if appropriate (e.g., FOLFOX and FOLFIRI or their variants) unless contraindicated, not tolerated, or declined.

• Male or female, age 18 or older

• ECOG performance status of 0 or 1

• Body weight \>30 kg

• Life expectancy of greater than 6 months

• 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 exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

⁃ 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).

• Patients must have acceptable organ and marrow function as defined below:

‣ Hemoglobin ≥9.0 g/dL

⁃ Absolute neutrophil count (ANC ≥1.0 x (\> 1000 per mm3))

⁃ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).

⁃ Total bilirubin : \< 2x upper limit of normal

⁃ AST (SGOT)/ALT (SGPT): \<2.5x institutional upper limit of normal

⁃ Creatinine: \<1.5x upper limit of normal OR Creatinine clearance \>40mL/min for patients with creatinine levels above institutional normal

⁃ Ability to understand and willingness to sign a written informed consent document

⁃ Residual or on-going ≥ Grade 3 treatment-related toxicity from previous chemotherapy should be resolved.