Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer

Inclusion Criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum. 2. Mismatch repair deficient or microsatellite instable (defined below), or POLE mutated tumors A. Mismatch repair deficient: loss of expression by immunohistochemical stains 4. ≥ 1 out of 4 markers (MLH1, MSH2, MSH6, PMS2) B. Microsatellite instable: loss of stability ≥2 out of 5 gene panels (BAT-25, BAT-26, D2S123, D5S345, D17S250) 3. Progressed after at least first-line systemic chemotherapy for metastatic setting. 4. ≥ 1 measurable lesion(s) by RECIST 1.1. 5. Unresectable advanced or metastatic disease. 6. Age over 20 years old. 7. ECOG 0-1, but final decision by clinical. 8. Adequate organ functions. A. Bone marrow function: Hemoglobin 9.0 g/dL, ANC 1,500/mm3, platelet 100,000/mm3 B. Hepatic functions: bilirubin ≤ 1.5 X ULN, AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN in cases of liver metastasis) C. Renal functions: serum Cr ≤ 1.5 X ULN or calculated CCr (Cockroft) ≥ 30 ml/min 9. Be willing and able to comply with the protocol for the duration of the study. 10. Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw the study at any time, without prejudice. 11. Female subjects must either be of non-reproductive potential ( 60 years old and no menses for 1 year without an alternative medical cause, or history of hysterectomy, or history of bilateral tubal ligation, or history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. 12. Women of childbearing potential and men must agree to use highly efficient contraception since signing of the IC form until at least 8 weeks after the last study drug administration. Exclusion Criteria: 1. Any prior treatment with PD-1 or PD-L1 inhibitor. 2. Receipt of the last dose of chemotherapy ≤ 28 days prior to the first dose of study drugs. 3. Current or prior use of immunosuppressive medication within 28 days before the first dose of avelumab, with the exceptions for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 4. Concurrent or previous history of another primary cancer within 3 years prior to randomisation except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis and pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the chief principal investigator. 5. Uncontrolled CNS metastases; permitted if asymptomatic or neurologically stable. 6. Prior radiation therapy would be permitted, but non-radiated evaluable lesions should be present at study entry. 7. Radiation therapy during study treatment is not permitted, but if the local investigator decides that radiation therapy should be given during study treatments, he should be convinced that there is no evidence of disease progression with agreement of the chief principal investigator. 8. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. 9. Active or prior documented autoimmune disease within the past 2 years; subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 10. Active or prior documented inflammatory bowel disease. 11. History of prior immunodeficiency. 12. History of allogeneic organ transplantation. 13. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3) 14. History of previous clinical diagnosis of active tuberculosis. 15. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines 16. Known history of testing positive for HIV 17. Hepatitis B virus (HBV) or hepatitis C virus(HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)Except, resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen) or Chronic HBV infection (as evidenced by detectable HBV surface antigen or HBV DNA). Subjects with chronic HBV infection must have HBV DNA \< 100 IU/mL and must be on antiviral therapy. 18. Major surgery or significant traumatic injury within 28 days prior to study treatment. 19. Non-healing wound, ulcer, or bone fracture. 20. Current evidence of significant gastrointestinal bleeding or (impending) obstruction. 21. Concomitant participation in another clinical trial. 22. Pregnant of breast-feeding subjects. Women of child-bearing potential must have pregnancy test within 7 days and a negative result must be documented before start of study treatment. 23. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results. 24. Active infection requiring systemic therapy. 25. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable. 26. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.