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Clinical Trial 20254

Cancer Type: Cutaneous
Study Type: Treatment
NCT#: NCT03787602

Phase: Phase II
Prinicipal Investigator: Brohl, Andrew

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Overview

Study Title

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 Naive

Summary

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.

Objective

To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy Secondary Objectives: To determine duration of response (DoR) - To determine progression-free survival (PFS) - To determine overall survival (OS) - To determine the pharmacokinetic/ pharmacodynamic (PK/PD) profile of KRT-232 - To determine KRT-232 safety and tolerability

Treatments

Therapies

Therapy (NOS)

Medications

Avelumab (); KRT-232 (); MSB00100718C (Avelumab)

Inclusion 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: (a) Hematologic: ANC ≥1.0 × 109/L in the absence of growth factors during the prior 7 days; platelet count ≥100 × 109/L (b) 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 (c) Renal: estimated creatinine clearance >30 mL/min by Cockcroft Gault.

  • Exclusion Criteria

    Exclusion Criteria:

  • Concurrent anticancer treatment such as chemotherapy, cytoreductive therapy, immune therapy, or cytokine therapy within 28 days or approximately 5 half-lives, whichever is shorter, 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
  • 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

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.