Pembrolizumab, Capecitabine, and Bevacizumab for Treating Colorectal Cancer

Inclusion Criteria

• Have histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinoma
• Have locally confirmed MSS or pMMR CRC; MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a PCR-based assay; pMMR is defined as presence of protein expression of 4 MMR enzymes (DNA mismatch repair protein Mlh1 (MLH1), DNA mismatch repair protein Msh2 (MSH2), mutS homolog 6 (MSH6) and Mismatch repair endonuclease postmeiotic segregation increased 2 (PMS2) by immunohistochemistry.
• Have stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine according to the interpretation of the treating provider
• Be willing and able to provide written informed consent/assent for the trial
• Be 18 years of age on day of signing informed consent
• Have measurable disease based on RECIST 1.1
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (phase II dose expansion cohort only); newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Demonstrate adequate organ function performed within 10 days of treatment initiation as defined below:
• Absolute neutrophil count (ANC) >= 1, 500 /mcL
• Platelets >= 100,000 / microliter (mcL)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine = = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)). Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin = 1.5 ULN. Patients with Gilbert's disease may be included if their direct bilirubin is ≤ 1.5 X ULN.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) = = 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) = 3 within 6 months of start of study drug
• Has greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1, then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPCR testing is not required
• Has a history of non-healing wounds or ulcers, or bone re-fractures within 3 months of fracture
• Has a history of arterial thromboembolism within 12 months of start of study drug
• Has inadequately controlled hypertension (defined as systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 95 mm Hg). The use of anti-hypertensive medications to control blood pressure is permitted. Retesting is permitted.
• Has a history of hypertensive crisis or hypertensive encephalopathy within 6 months prior to planned start of study drug
• Has had clinically significant cardiovascular disease within 12 months of planned start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
• Has a known history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned start