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

February 28, 2023 updated by: Kartos Therapeutics, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
115

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
      • Woolloongabba, Australia
        • Recruiting
        • Princess Alexandra Hospital Oncology
  • Brazil
      • Blumenau, Brazil
        • Recruiting
        • Centro Catarinense de Pesquisa (CECAP) - Hospital Santa Catarina de Blumenau
      • Brasília, Brazil
        • Recruiting
        • Instituto Nacional do Câncer
      • Curitiba, Brazil
        • Recruiting
        • Centro Intergado de Oncologia
      • Ijuí, Brazil
        • Recruiting
        • Centro de Pesquisa Clinica em Oncologia
      • Itajai, Brazil
        • Recruiting
        • Clinica de Neoplasias Litoral
      • São Paulo, Brazil
        • Recruiting
        • Hospital Paulistano
  • Canada
      • Toronto, Canada
        • Recruiting
        • Princess Margaret Cancer Centre
  • France
      • Bordeaux, France
        • Recruiting
        • CHU de Bordeaux- Hôpital Saint-André
      • Gif-sur-Yvette, France
        • Recruiting
        • AP-HP Universite Paris Saclay
      • Lille, France
        • Recruiting
        • CHU de Lille
      • Lyon, France
        • Recruiting
        • Chu Lyon-Sud
      • Marseille, France, Cedex 5
        • Recruiting
        • Hôpital de la Timone. Aix-Marseille Université
      • Montpellier, France
        • Recruiting
        • CHU Montpellier
      • Nantes, France
        • Recruiting
        • CHU de Nantes
      • Paris, France
        • Recruiting
        • Hôpital Saint Louis - APHP
      • Tours, France
        • Recruiting
        • Chu De Tours
  • Germany
      • Berlin, Germany
        • Recruiting
        • Vivantes Network for Health Gmb, Neukölln Clinic
      • Erlangen, Germany
        • Recruiting
        • Universitätsklinikum Erlangen
      • Essen, Germany
        • Recruiting
        • Universitätsklinikum Essen (AöR)
      • Heidelberg, Germany
        • Recruiting
        • Nationales Centrum für Tumorerkrankungen NCT
      • Köln, Germany
        • Recruiting
        • Uniklinik Köln
      • Rostock, Germany
        • Recruiting
        • Universitätsklinik Rostock
      • Tübingen, Germany
        • Recruiting
        • Universitäts-Hautklinik Tübingen
  • Italy
      • Candiolo, Italy
        • Recruiting
        • Institute for Cancer Research and Treatment
      • Napoli, Italy
        • Recruiting
        • Istituto Nazionale Tumori Irccs Fondazione Pascale
      • Ravenna, Italy
        • Recruiting
        • AUSL della Romagna
      • Siena, Italy
        • Recruiting
        • AOUS Le Scotte
      • Verona, Italy
        • Recruiting
        • OSP Civile Maggiore Borgo Trento
  • Korea, Republic of
      • Goyang-si, Korea, Republic of
        • Recruiting
        • National Cancer Center
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Severance Hospital Yonsei University Health System
  • Netherlands
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Duran i Reynals
      • Madrid, Spain
        • Recruiting
        • Hospital General Universitario Gregorio Marañn (Madrid)
      • Pamplona, Spain
        • Recruiting
        • Complejo Hospitalario de Navarra
      • Valencia, Spain
        • Recruiting
        • Fundacio Investigao Hospital General Universitario de Valencia
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Anschutz Medical Campus
    • Florida
      • Miami, Florida, United States, 33176
        • Recruiting
        • Miami Cancer Institute
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Northwestern Memorial Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Healthcare
        • Contact:
          • Norton Cancer Institute Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215-5418
        • Recruiting
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2434
        • Active, not recruiting
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Health Care Services

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1, Arm 1
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 1, Arm 1b
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 1, Arm 2b
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 1, Arm 3
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 1, Arm 5
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 1 Expansion
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 2, Arm 1 KRT-232 in combination with avelumab
KRT-232 will be administered orally, once daily (QD) on Days 1-5, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Drug: Avelumab
Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
Other Names:
  • Bavencio
Experimental: Cohort 2, Arm 2 KRT-232 in combination with avelumab
KRT-232 will be administered orally, once daily (QD) on Days 1-7, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Drug: Avelumab
Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
Other Names:
  • Bavencio
Experimental: Cohort 2 Expansion
KRT-232 will be administered orally, once daily (QD) per RP2D dose and schedule, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Drug: Avelumab
Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
Other Names:
  • Bavencio
Experimental: Cohort 3
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin
Experimental: Cohort 4
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Drug: KRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
  • navtemadlin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cohort 1 Part 1: To determine the KRT-232 RP2D.
Time Frame: 10 Weeks
The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.
10 Weeks
Cohort 1 Part 2: 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: 10 Weeks
ORR will be assessed per RECIST criteria version 1.1 after all subjects have been treated at the RP2D of KRT 232 and completed the second response assessment.
10 Weeks
Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab
Time Frame: 28 Days
DLTs will be used to establish the MTD of KRT-232 in combination with avelumab. SRC will determine the RP2D based on the safety of combination of KRT-232 with avelumab.
28 Days
Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC
Time Frame: 10 Weeks
ORR will be assessed per RECIST criteria version 1.1 after all 30 subjects have been treated at the RP2D of in combination with avelumab and have completed the second response assessment.
10 Weeks
Cohort 3: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC are chemotherapy naive and have failed anti-PD-1/PD-L.
Time Frame: 10 Weeks
ORR will be assessed per RECIST criteria 1.1 by IRC.
10 Weeks
Cohort 4: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and have had least 1 line of prior chemotherapy.
Time Frame: 10 Weeks
ORR will be assessed per RECIST criteria 1.1 by IRC.
10 Weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To determine the confirmed ORR based on investigator assessment.
Time Frame: 1 year after last subject enrolled.
ORR will be assessed per RECIST criteria 1.1 by investigators.
1 year after last subject enrolled.
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.
1 year after last subject enrolled
To determine Progression-free survival (PFS)
Time Frame: 1 year after last subject enrolled
Time from initial treatment until disease progression.
1 year after last subject enrolled
To determine overall survival (OS)
Time Frame: 1 year after last subject enrolled
Time from initial treatment until death from any cause.
1 year after last subject enrolled
To determine clinical benefit rate (CBR)
Time Frame: 1 year after last subject enrolled.
PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.
1 year after last subject enrolled.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 19, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KRT-232-103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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