Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases

PRIMARY OBJECTIVE: I. To characterize the change in the populations of tumor infiltrating lymphocytes (TILs) induced by neoadjuvant pembrolizumab plus vactosertib in participants with metastatic colorectal cancer (mCRC). SECONDARY OBJECTIVES: I. To establish the safety/toxicity profile of pembrolizumab-based treatment in the perioperative setting for participants with colorectal cancer (CRC) with resectable hepatic metastases. II. To explore the efficacy of pembrolizumab plus vactosertib in participants with CRC with resectable hepatic metastases. EXPLORATORY OBJECTIVES: I. To determine the impact of pembrolizumab-based treatment on programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating immune cells (TIICs), in participants with mCRC. II. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based treatment in participants with mCRC. III. To explore molecular profiles to identify potentially predictive biomarkers for participants with metastatic CRC treated with immunotherapy (including but not limited to microsatellite instability (MSI) testing). IV. To correlate change in TIICs, PD-L1 expression, and T cell repertoires as well as molecular profiles with response/resistance and toxicity. V. To identify immune response messenger ribonucleic acid (mRNA) expression analysis to derive signatures associated with tumor response. VI. To identify genomic mutations and gene copy aberrations associated with response and resistance to therapy. VII. To correlate changes in microbiome composition and diversity with diet and lifestyle factors. OUTLINE: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and vactosertib orally (PO) once a day (QD) for the first cycle 5 days a week for 2 weeks. Participants then undergo standard of care surgical removal of liver metastases approximately 2 weeks (minimum 1 week) after last dose of vactosertib. OPTIONAL ADJUVANT TREATMENT: After surgery, eligible participants may also receive pembrolizumab and vactosertib every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants who do not undergo optional adjuvant treatment are followed up at 14 days and then every 90 days for up to 1 year. Participants who undergo optional adjuvant treatment are followed up at 30 days and then every 90 days for up to 2 years.