Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a poor prognosis in patients with advanced disease, with mortality as high as 46%. An oncogenic Merkel cell polyomavirus (MCPyV) is present in about 80% of MCC tumors, which inactivates tumor suppressors p53 and RB. Virus-positive MCC has proven to be an immunologically responsive disease and the recently approved PD-L1 inhibitor avelumab (March 2017) has improved the prognosis of patients with advanced MCC. However, despite the addition of immune checkpoint inhibitors to the treatment paradigm, a lack of response or disease progression occurs in up to two-thirds of avelumab patients previously treated with chemotherapy, and 32-44% of first-line patients treated with the PD-1 inhibitors nivolumab or pembrolizumab. KRT-232 is a potent and selective small molecule targeted drug that binds to murine double minute chromosome 2 (MDM2) and inhibits the MDM2/tumor protein 53 (p53) protein-protein interaction. Inactivating mutations in p53 have rarely been found in MCC, and the majority of MCCs with the presence of MCPyV express p53^WT. The purpose of this study is to evaluate the tolerability and efficacy of KRT-232 in p53WT MCC patients who have been treated with anti-PD-1/L1 immunotherapy. Methods: The primary objective is ORR by RECIST v1.1 after 2 cycles (42 days) as determined by independent review. A Simon two-stage design is employed. In Stage 1, up to 13 eligible patients will be enrolled and treated with 240 mg KRT-232 once daily (QD) on Days 1-7 of a 21-day cycle. If the predesignated efficacy threshold is reached in Stage 1, enrollment for Stage 2 will include an additional 14 patients (for a total of 27 patients). The study is enrolling in the U.S. Clinical trial information: NCT03787602