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

Study 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 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03787602
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Kartos Therapeutics, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, Brazil, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Merkel Cell Carcinoma
Arms & Interventions

Arms

Experimental: Cohort 1, Arm 1

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

Experimental: Cohort 1, Arm 1b

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.

Experimental: Cohort 1, Arm 2b

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.

Experimental: Cohort 1, Arm 3

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

Experimental: Cohort 1, Arm 5

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.

Experimental: Cohort 1 Expansion

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

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.

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.

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.

Experimental: Cohort 3

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

Experimental: Cohort 4

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

Interventions

Drug: - KRT-232

KRT-232 is an experimental MDM2 anticancer drug taken by mouth.

Drug: - Avelumab

Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Aurora, Colorado

Status

Recruiting

Address

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045

Miami Cancer Institute, Miami, Florida

Status

Recruiting

Address

Miami Cancer Institute

Miami, Florida, 33176

Moffitt, Tampa, Florida

Status

Recruiting

Address

Moffitt

Tampa, Florida, 33612

Northwestern Memorial Hospital, Chicago, Illinois

Status

Recruiting

Address

Northwestern Memorial Hospital

Chicago, Illinois, 60612

Norton Healthcare, Louisville, Kentucky

Status

Recruiting

Address

Norton Healthcare

Louisville, Kentucky, 40202

Site Contact

Norton Cancer Institute Research

jmei@kartosthera.com

650-542-0136

Massachusetts General Hospital, Boston, Massachusetts

Status

Recruiting

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215-5418

University of Michigan, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan

Ann Arbor, Michigan, 48109

Memorial Sloan-Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021

Mount Sinai Hospital, New York, New York

Status

Recruiting

Address

Mount Sinai Hospital

New York, New York, 10029

Fox Chase Cancer Center, Philadelphia, Pennsylvania

Status

Active, not recruiting

Address

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2434

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania

Status

Recruiting

Address

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

University of Texas MD Anderson, Houston, Texas

Status

Recruiting

Address

University of Texas MD Anderson

Houston, Texas, 77030

Inova Health Care Services, Fairfax, Virginia

Status

Recruiting

Address

Inova Health Care Services

Fairfax, Virginia, 22031

International Sites

Princess Alexandra Hospital Oncology, Woolloongabba, Australia

Status

Recruiting

Address

Princess Alexandra Hospital Oncology

Woolloongabba, ,

Blumenau, Brazil

Status

Recruiting

Address

Centro Catarinense de Pesquisa (CECAP) - Hospital Santa Catarina de Blumenau

Blumenau, ,

Instituto Nacional do Cancer, Brasília, Brazil

Status

Recruiting

Address

Instituto Nacional do Cancer

Brasília, ,

Centro Intergado de Oncologia, Curitiba, Brazil

Status

Recruiting

Address

Centro Intergado de Oncologia

Curitiba, ,

Centro de Pesquisa Clinica em Oncologia, Ijuí, Brazil

Status

Recruiting

Address

Centro de Pesquisa Clinica em Oncologia

Ijuí, ,

Clinica De Neoplasias Litoral, Itajai, Brazil

Status

Recruiting

Address

Clinica De Neoplasias Litoral

Itajai, ,

Hospital Paulistano, São Paulo, Brazil

Status

Recruiting

Address

Hospital Paulistano

São Paulo, ,

Princess Margaret Cancer Centre, Toronto, Canada

Status

Recruiting

Address

Princess Margaret Cancer Centre

Toronto, ,

CHU de Bordeaux- Hopital Saint-Andre, Bordeaux, France

Status

Recruiting

Address

CHU de Bordeaux- Hopital Saint-Andre

Bordeaux, ,

AP-HP Universite Paris Saclay, Gif-sur-Yvette, France

Status

Recruiting

Address

AP-HP Universite Paris Saclay

Gif-sur-Yvette, ,

CHU de Lille, Lille, France

Status

Recruiting

Address

CHU de Lille

Lille, ,

CHU Lyon-Sud, Lyon, France

Status

Recruiting

Address

CHU Lyon-Sud

Lyon, ,

Marseille, France

Status

Recruiting

Address

Hôpital de la Timone. Aix-Marseille Université

Marseille, , Cedex 5

CHU Montpellier, Montpellier, France

Status

Recruiting

Address

CHU Montpellier

Montpellier, ,

CHU de Nantes, Nantes, France

Status

Recruiting

Address

CHU de Nantes

Nantes, ,

Hôpital Saint Louis - APHP, Paris, France

Status

Recruiting

Address

Hôpital Saint Louis - APHP

Paris, ,

CHU de Tours, Tours, France

Status

Recruiting

Address

CHU de Tours

Tours, ,

Berlin, Germany

Status

Recruiting

Address

Vivantes Network for Health Gmb, Neukölln Clinic

Berlin, ,

Universitätsklinikum Erlangen, Erlangen, Germany

Status

Recruiting

Address

Universitätsklinikum Erlangen

Erlangen, ,

Universitätsklinikum Essen (AöR), Essen, Germany

Status

Recruiting

Address

Universitätsklinikum Essen (AöR)

Essen, ,

Heidelberg, Germany

Status

Recruiting

Address

Nationales Centrum für Tumorerkrankungen NCT

Heidelberg, ,

Uniklinik Koln, Köln, Germany

Status

Recruiting

Address

Uniklinik Koln

Köln, ,

Universitätsklinik Rostock, Rostock, Germany

Status

Recruiting

Address

Universitätsklinik Rostock

Rostock, ,

Universitats-Hautklinik Tubingen, Tübingen, Germany

Status

Recruiting

Address

Universitats-Hautklinik Tubingen

Tübingen, ,

Candiolo, Italy

Status

Recruiting

Address

Institute for Cancer Research and Treatment

Candiolo, ,

Napoli, Italy

Status

Recruiting

Address

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, ,

AUSL della Romagna, Ravenna, Italy

Status

Recruiting

Address

AUSL della Romagna

Ravenna, ,

AOUS Le Scotte, Siena, Italy

Status

Recruiting

Address

AOUS Le Scotte

Siena, ,

OSP Civile Maggiore Borgo Trento, Verona, Italy

Status

Recruiting

Address

OSP Civile Maggiore Borgo Trento

Verona, ,

National Cancer Center, Goyang-si, Korea, Republic of

Status

Recruiting

Address

National Cancer Center

Goyang-si, ,

Seoul National University Hospital, Seoul, Korea, Republic of

Status

Recruiting

Address

Seoul National University Hospital

Seoul, ,

Seoul, Korea, Republic of

Status

Recruiting

Address

Severance Hospital Yonsei University Health System

Seoul, ,

University Medical Center Groningen, Groningen, Netherlands

Status

Recruiting

Address

University Medical Center Groningen

Groningen, ,

Hospital Duran i Reynals, Barcelona, Spain

Status

Recruiting

Address

Hospital Duran i Reynals

Barcelona, ,

Madrid, Spain

Status

Recruiting

Address

Hospital General Universitario Gregorio Marañn (Madrid)

Madrid, ,

Complejo Hospitalario de Navarra, Pamplona, Spain

Status

Recruiting

Address

Complejo Hospitalario de Navarra

Pamplona, ,

Valencia, Spain

Status

Recruiting

Address

Fundacio Investigao Hospital General Universitario de Valencia

Valencia, ,

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