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

Status: In Review

Description

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. Inhibition of MDM2 is a novel mechanism of action in MCC. This study is Phase 2, Open-Label, Single-Arm Study of KRT-232 in Patients with p53 Wild-Type (p53WT) Merkel Cell Carcinoma

Eligibility Criteria

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

Locations & Contacts

Colorado

Aurora
University of Colorado Hospital
Status: Approved
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Approved
Name Not Available

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Kartos Therapeutics, Inc.

Trial IDs

Primary ID KRT-232-103
Secondary IDs NCI-2019-00044
Clinicaltrials.gov ID NCT03787602