Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale within 14 days prior to registration.
• Have histological or cytological evidence of colorectal adenocarcinoma with confirmation of metastatic disease either by pathologic or radiologic findings.
• Have identified tissue from an archival tissue sample (preferably from a metastasis, but sample from primary tumor allowable) or newly obtained core or excisional biopsy of a tumor lesion.
• Have had no prior systemic therapy for advanced or metastatic disease. Prior adjuvant therapy should have been completed at least 9 months from documentation of metastatic disease. Prior palliative radiotherapy allowed if toxicities resolved to grade 1 or baseline.
• Have measurable disease according to RECIST v1.1 obtained by imaging within 28 days prior to registration.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 14 days prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Subjects of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) are those who meet the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; OR has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication

Exclusion Criteria

• Has clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of registration. Subjects are not permitted to participate in another investigational drug study while being treated on this protocol.
• Is unable to receive a port or peripherally inserted central catheter (PICC).
• Has a diagnosis of immunodeficiency or is receiving chronic steroid therapy of prednisone ≥ 10 mg daily or any equivalent dose of corticosteroids.
• Has previously undergone organ or bone marrow transplantation and is on immunosuppressive therapy
• Has had major surgery or significant traumatic injury within 4 weeks of study registration. Subjects must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. A diagnostic or research biopsy does not exclude subjects from enrollment. Placement of a vascular access device such as a Port-A-Cath is not considered major surgery
• Has baseline peripheral neuropathy/paresthesia grade ≥ 1.
• Has a known additional malignancy within the past 3 years. Exceptions include treated localized basal cell or squamous cell carcinoma of the skin, in situ cervical or vulvar carcinoma that has undergone potentially curative therapy, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer (Gleason sore 6). Any cancer curatively treated > 3 years prior to registration with no clinical evidence of recurrence is permitted
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously