Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed metastatic colorectal cancer.
• Patients must have measurable disease per RECIST v1.1 criteria.
• Patients must have had at least prior treatment with a fluoropyrimidine and either oxaliplatin or irinotecan.
• Age >/=18 years. Because no dosing or adverse event data are currently available on the use of this combination in patients 30kg.
• Life expectancy of greater than 6 months.
• ECOG performance status 0-1 (Karnofsky >/=70%).
• Patients must have normal organ and marrow function as defined below: - Leukocytes >/=3,000/mcL, Absolute neutrophil count >/=1,500/mcL, Hemoglobin >/=9.0g/dL, Platelets >/=75,000/mcL, Total bilirubin 40mL/min by Cockcroft-Gault or 24h urine collection.
• Known MSS status by either IHC or PCR. Known or evaluable BRAF and KRAS status.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. 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).
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately and will be removed from the study.
• Ability to understand and the willingness to sign a written informed consent document.
• Willingness to have 2 tumor biopsies; the first before and the second while on therapy (optional for all patients and may become mandatory in order to ensure 15 patients at MTD have paired biopsies).

Exclusion Criteria

• Patients who have had chemotherapy within 2 weeks prior to first dose of study drug.
• Any unresolved toxicity NCI CTCAE Grade >/=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: -- Subjects with Grade >/=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal investigator.-- Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal investigator.
• Patients may not be receiving any other investigational agents.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• Patients with known brain metastases or leptomeningeal carcinomatosis will be excluded from this clinical trial. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
• Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
• History of pneumonitis or interstitial lung disease (ILD).
• History of allogenic organ transplantation.
• Subjects with active, known, or suspected autoimmune disease including patients with a history of inflammatory bowel disease (ulcerative colitis or Crohn's disease); patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis