This Study Evaluates KRT-232, a Novel Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients With (p53WT) Merkel Cell Carcinoma Who Have Failed Anti-PD-1/ PD-L1 Immunotherapy

Inclusion Criteria:

- ECOG performance status of 0 to 1

- Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable
lesion by RECIST 1.1

- MCC expressing p53WT based on any CLIA or FDA approved test

- Patients must have failed (i.e., relapsed or were refractory to) treatment with at
least one PD-1 inhibitor or PD-L1 inhibitor for MCC

- Fresh or archival tumor tissue must be submitted for biomarker assessment. Archival
tissue samples must have been obtained from biopsy performed ≤ 2 years before the date
of signing the informed consent for this study. Adequate hematological, hepatic, and
renal function within 14 days prior to the first dose of KRT-232:

1. Hematologic: ANC ≥1.0 × 109/L in the absence of growth factors during the prior 7
days; platelet count ≥100 × 109/L

2. Hepatic: total bilirubin ≤2.0 times the upper limit of normal (ULN), unless
Gilbert's Syndrome; aspartate transaminase/serum glutamic oxaloacetic
transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic
transaminase (ALT/SGPT) ≤2.5 ULN

3. Renal: estimated creatinine clearance >45 mL/min by Cockcroft Gault:

Exclusion Criteria:

- Concurrent anticancer treatment such as chemotherapy, cytoreductive therapy, immune
therapy, or cytokine therapy within 28 days or approximately 5 half-lives prior to the
first dose of KRT-232

- Radiation therapy within 2 weeks prior to the first dose of KRT-232

- Toxicity from prior radiation therapy that has not resolved to National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 0 or Grade
1 (with the exception of Grade 2 alopecia)

- Participation in another interventional clinical trial within the past 4 weeks of the
first dose of KRT-232

- Prior treatment for MCC with histone deacetylase (HDAC) inhibitors or BCL-2 inhibitors

- Patients previously treated with MDM2 antagonist therapies or p53-directed therapies

- History of major organ transplant

- Patients with known central nervous system (CNS) metastases that are previously
untreated