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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

NCT03787602

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

Related Conditions:
  • Merkel Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase 2, Open-Label, Single-Arm Study 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

Clinical Trial IDs

  • ORG STUDY ID: KRT-232-103
  • NCT ID: NCT03787602

Conditions

  • Merkel Cell Carcinoma

Interventions

DrugSynonymsArms
KRT-232Single Arm

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalKRT-232 will be administered at a dose of 240 mg rally once daily (QD) on Days 1-7 of a 21-day cycle.
  • KRT-232

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:

               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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy
Time Frame:42 days
Safety Issue:
Description:The proportion of patients achieving a CR or PR as determined by RECIST 1.1 after 2 cycles of treatment

Secondary Outcome Measures

Measure:To determine the duration of response (DoR)
Time Frame:1 year after last subject enrolled
Safety Issue:
Description:Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression
Measure:To determine Progression-free survival (PFS)
Time Frame:1 year after last subject enrolled
Safety Issue:
Description:Time from initial treatment until disease progression
Measure:To determine overall survival (OS)
Time Frame:1 year after last subject enrolled
Safety Issue:
Description:Time from initial treatment until death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Kartos Therapeutics, Inc.

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