Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma

A Phase 1b/2, Open-Label Study Evaluating the Safety and Efficacy of KRT-232 in Patients With p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC) Who Have Failed Anti-PD-1 or Anti-PD-L1 Immunotherapy, or in Combination With Avelumab in MCC Patients Who Are Anti-PD-1 or Anti-PD-L1 Treatment Naïve

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Merkel Cell Carcinoma (MCC) who have failed treatment with at least one anti-PD-1 or anti-PD-L1 immunotherapy or in combination with avelumab in MCC patients who are anti-PD-1 or anti-PD-L1 treatment naïve. Inhibition of MDM2 is a novel mechanism of action in MCC.

Inclusion Criteria:

• For Cohort 1, 3 and 4 patients must have failed treatment with at least one PD-1 inhibitor or PD-L1 inhibitor for metastatic MCC
• For Cohort 2, patients must not have received any anti-PD-1 or anti-PD-L1 therapy
• For Cohort 3, patients must not have received any prior chemotherapy
• For Cohort 4, patients must have received at least one prior line of chemotherapy
• 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 test approved by local health authority or a validated test (Cohort 1 and 2)
• MCC expressing p53WT based Central Lab test (Cohort 3 and 4)
• Adequate hematological, hepatic, and renal functions

Exclusion Criteria:

• For Cohort 2, subjects must not have autoimmune disease, medical conditions requiring systemic immunosuppression, prior stem cell transplant, or active infection with HBV or HCV.
• 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
• Grade 2 or higher QTc prolongation (>480 milli-seconds per NCI-CTCAE criteria, version 5.0)