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Merkel Cell CarcinomaPhase 1/2NCT03787602

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

A Phase 1/2 study testing KRT-232 and Avelumab in people with Merkel Cell Carcinoma, run by Kartos Therapeutics, Inc. at 51 sites in 10 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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 or in combination with avelumab in MCC patients who are anti-PD-1 or anti-PD-L1 treatment naïve. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Merkel Cell Carcinoma
What is being tested?
KRT-232 and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
51 sitesin 10 countries
Study dates
19 Mar 2019to Aug 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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 locations and contacts

51 sites in 10 countries.

John Mei contact

650-542-0136

jmei@kartosthera.com

Emily Houlihan contact

401-954-8042

ehoulihan@kartosthera.com

51 sites in 10 countries

United States14 sites, 13 recruiting

  • University of Michigan

    Ann Arbor, Michigan, 48109

    Recruiting

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215-5418

    Recruiting

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60612

    Recruiting

  • Inova Health Care Services

    Fairfax, Virginia, 22031

    Recruiting

  • University of Texas MD Anderson

    Houston, Texas, 77030

    Recruiting

  • Norton Healthcare

    Louisville, Kentucky, 40202

    Norton Cancer Institute Research

    Recruiting

  • Miami Cancer Institute

    Miami, Florida, 33176

    Recruiting

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

    Recruiting

  • Mount Sinai Hospital

    New York, New York, 10029

    Recruiting

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2434

    Active, not recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Recruiting

  • Moffitt

    Tampa, Florida, 33612

    Recruiting

Other trials in United States

France9 sites, 9 recruiting

  • CHU de Bordeaux- Hopital Saint-Andre

    Bordeaux

    Recruiting

  • AP-HP Universite Paris Saclay

    Gif-sur-Yvette

    Recruiting

  • CHU de Lille

    Lille

    Recruiting

  • CHU Lyon-Sud

    Lyon

    Recruiting

  • Hôpital de la Timone. Aix-Marseille Université

    Marseille, Cedex 5

    Recruiting

  • CHU Montpellier

    Montpellier

    Recruiting

  • CHU de Nantes

    Nantes

    Recruiting

  • Hôpital Saint Louis - APHP

    Paris

    Recruiting

  • CHU de Tours

    Tours

    Recruiting

Other trials in France

Germany7 sites, 7 recruiting

  • Vivantes Network for Health Gmb, Neukölln Clinic

    Berlin

    Recruiting

  • Uniklinik Koln

    Cologne

    Recruiting

  • Universitätsklinikum Erlangen

    Erlangen

    Recruiting

  • Universitätsklinikum Essen (AöR)

    Essen

    Recruiting

  • Nationales Centrum für Tumorerkrankungen NCT

    Heidelberg

    Recruiting

  • Universitätsklinik Rostock

    Rostock

    Recruiting

  • Universitats-Hautklinik Tubingen

    Tübingen

    Recruiting

Other trials in Germany

Brazil6 sites, 6 recruiting

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

    Blumenau

    Recruiting

  • Instituto Nacional do Cancer

    Brasília

    Recruiting

  • Centro Intergado de Oncologia

    Curitiba

    Recruiting

  • Centro de Pesquisa Clinica em Oncologia

    Ijuí

    Recruiting

  • Clinica De Neoplasias Litoral

    Itajaí

    Recruiting

  • Hospital Paulistano

    São Paulo

    Recruiting

Other trials in Brazil

Italy5 sites, 5 recruiting

  • Institute for Cancer Research and Treatment

    Candiolo

    Recruiting

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale

    Naples

    Recruiting

  • AUSL della Romagna

    Ravenna

    Recruiting

  • AOUS Le Scotte

    Siena

    Recruiting

  • OSP Civile Maggiore Borgo Trento

    Verona

    Recruiting

Other trials in Italy

Spain4 sites, 4 recruiting

  • Hospital Duran i Reynals

    Barcelona

    Recruiting

  • Hospital General Universitario Gregorio Marañn (Madrid)

    Madrid

    Recruiting

  • Complejo Hospitalario de Navarra

    Pamplona

    Recruiting

  • Fundacio Investigao Hospital General Universitario de Valencia

    Valencia

    Recruiting

Other trials in Spain

South Korea3 sites, 3 recruiting

  • National Cancer Center

    Goyang-si

    Recruiting

  • Seoul National University Hospital

    Seoul

    Recruiting

  • Severance Hospital Yonsei University Health System

    Seoul

    Recruiting

Other trials in South Korea

Australia1 site, 1 recruiting

  • Princess Alexandra Hospital Oncology

    Woolloongabba

    Recruiting

Other trials in Australia

Canada1 site, 1 recruiting

  • Princess Margaret Cancer Centre

    Toronto

    Recruiting

Other trials in Canada

Netherlands1 site, 1 recruiting

  • University Medical Center Groningen

    Groningen

    Recruiting

Other trials in Netherlands

About this study

Official 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 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.

Being tested
KRT-232, Avelumab
Keywords
navtemadlin (KRT-232)
Medical subject headings
Carcinoma, Merkel Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KRT-232Drug

    Also called navtemadlin

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

  • AvelumabDrug

    Also called Bavencio

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

Study groups in NCT03787602
Study groupRoleWhat they receive
Cohort 1, Arm 1ExperimentalKRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Receives: Drug: KRT-232
Cohort 1, Arm 1bExperimentalKRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
Receives: Drug: KRT-232
Cohort 1, Arm 2bExperimentalKRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
Receives: Drug: KRT-232
Cohort 1, Arm 3ExperimentalKRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Receives: Drug: KRT-232
Cohort 1, Arm 5ExperimentalKRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
Receives: Drug: KRT-232
Cohort 1 ExpansionExperimentalKRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Receives: Drug: KRT-232
Cohort 2, Arm 1 KRT-232 in combination with avelumabExperimentalKRT-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.
Receives: Drug: KRT-232; Drug: Avelumab
Cohort 2, Arm 2 KRT-232 in combination with avelumabExperimentalKRT-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.
Receives: Drug: KRT-232; Drug: Avelumab
Cohort 2 ExpansionExperimentalKRT-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.
Receives: Drug: KRT-232; Drug: Avelumab
Cohort 3ExperimentalKRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Receives: Drug: KRT-232
Cohort 4ExperimentalKRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Receives: Drug: KRT-232

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cohort 1 Part 1: To determine the KRT-232 RP2D.

    The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.

    Measured: 10 Weeks

  2. 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

    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.

    Measured: 10 Weeks

  3. Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab

    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.

    Measured: 28 Days

  4. Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC

    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.

    Measured: 10 Weeks

  5. 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.

    ORR will be assessed per RECIST criteria 1.1 by IRC.

    Measured: 10 Weeks

  6. 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.

    ORR will be assessed per RECIST criteria 1.1 by IRC.

    Measured: 10 Weeks

Secondary outcomes (5)

  1. To determine the confirmed ORR based on investigator assessment.

    ORR will be assessed per RECIST criteria 1.1 by investigators.

    Measured: 1 year after last subject enrolled.

  2. To determine the duration of response (DoR)

    Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression.

    Measured: 1 year after last subject enrolled

  3. To determine Progression-free survival (PFS)

    Time from initial treatment until disease progression.

    Measured: 1 year after last subject enrolled

  4. To determine overall survival (OS)

    Time from initial treatment until death from any cause.

    Measured: 1 year after last subject enrolled

  5. To determine clinical benefit rate (CBR)

    PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.

    Measured: 1 year after last subject enrolled.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2018
  2. Study start19 Mar 2019
  3. Primary completionNov 2024 (estimated)
  4. Study completionAug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03787602
Sponsor's protocol ID
KRT-232-103
Status last verified
Feb 2023
First submitted
6 Dec 2018
Last updated
2 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KRT-232 and Avelumab in people with Merkel Cell Carcinoma, run by Kartos Therapeutics, Inc. at 51 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States, France, Germany, Brazil, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact John Mei (650-542-0136, jmei@kartosthera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1 Part 1: To determine the KRT-232 RP2D. (time frame: 10 Weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03787602.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2023.

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