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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

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ClinicalTrials.gov Identifier: NCT03787602
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Brief 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.

This study is Phase 2, Open-Label, Single-Arm Study of KRT-232 in Patients with p53 Wild-Type (p53WT) Merkel Cell Carcinoma


Condition or disease Intervention/treatment Phase
Merkel Cell Carcinoma Drug: KRT-232 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: Single Arm
KRT-232 will be administered at a dose of 240 mg rally once daily (QD) on Days 1-7 of a 21-day cycle.
Drug: KRT-232
KRT-232, administered by mouth




Primary Outcome Measures :
  1. 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 ]
    The proportion of patients achieving a CR or PR as determined by RECIST 1.1 after 2 cycles of treatment


Secondary Outcome Measures :
  1. To determine the duration of response (DoR) [ Time Frame: 1 year after last subject enrolled ]
    Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression

  2. To determine Progression-free survival (PFS) [ Time Frame: 1 year after last subject enrolled ]
    Time from initial treatment until disease progression

  3. To determine overall survival (OS) [ Time Frame: 1 year after last subject enrolled ]
    Time from initial treatment until death from any cause



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787602


Contacts
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Contact: John Mei 650-542-0136 jmei@kartosthera.com

Locations
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United States, Colorado
Regents of the University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Carolyn Dilz    720-848-0584    carolyn.dilz@ucdenver.edu   
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60612
Contact: Lauren Nielsen       RHLCCCTrialStartup@northwestern.edu   
United States, Kentucky
Norton Healthcare Recruiting
Louisville, Kentucky, United States, 40202
Contact: Jayne Carwile       Jayne.Carwile@nortonhealthcare.org   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Harita Dharaneeswaran    617-632-4189    Harita_Dharaneeswaran@DFCI.HARVARD.EDU   
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215-5418
Contact: Sarah Garcia    617-632-2987    Sarah_Garcia@DFCI.HARVARD.EDU   
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: John Surgeon       john-tod.surgeon2@mssm.edu   
United States, Missouri
Washington University School of Medicine in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Puspanjali Bhatta         
Contact    (314) 286-0896    pbhatta@wustl.edu   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Natasha Martin       martinn@mskcc.org   
Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Jennifer Perez       jennifer.perez2@mssm.edu   
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2434
Contact: April King       April.King@fccc.edu   
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Scarlett Ernst         
Contact    (412) 623-4115    ernstsj2@upmc.edu   
United States, Texas
University of Texas MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Chanel Smith    713-563-3835    CCSmith@mdanderson.org   
United States, Virginia
Inova Health Care Services Recruiting
Fairfax, Virginia, United States, 22031
Contact: Wendy Crego       wendy.crego@inova.org   
Sponsors and Collaborators
Kartos Therapeutics, Inc.

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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03787602     History of Changes
Other Study ID Numbers: KRT-232-103
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue