Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer

April 12, 2024 updated by: Kartos Therapeutics, Inc.

A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy

This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy.

The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

268

Phase

  • Phase 2
  • Phase 3

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 Locations

  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • University Hospital Graz, Department of Gynecology and Obstetrics
        • Contact:
          • Edgar Petru
      • Innsbruck, Austria, 6020
        • Recruiting
        • Medizinische Universität Innsbruck
        • Contact:
          • Christian Marth
      • Vienna, Austria, 1090
        • Recruiting
        • Medizinische Universität Wien
        • Contact:
          • Stephan Polterauer
  • Denmark
      • Odense, Denmark, DK-5000
        • Recruiting
        • Odense University Hospital
  • Estonia
      • Tartu, Estonia, 50406
        • Recruiting
        • Tartu University Hospital
        • Contact:
          • Kristiina Ojamaa
  • Finland
      • Kuopio, Finland, 70200
        • Recruiting
        • Kuopio University Hospital
      • Turku, Finland, 20520
        • Recruiting
        • Turku University Hospital
  • Georgia
      • Batumi, Georgia, 6000
        • Recruiting
        • LTD High Technology Hospital Medcenter
        • Contact:
          • Tamta Makharadze
      • Tbilisi, Georgia, 0102
        • Recruiting
        • American Hospital Network LLC
        • Contact:
          • Zaza Tsitsishvili
      • Tbilisi, Georgia, 0186
        • Recruiting
        • Caucasus Medical Centre
        • Contact:
          • Lika Katselashvili
  • Hungary
      • Budapest, Hungary, H-1122
        • Recruiting
        • National Institute of Oncology
      • Debrecen, Hungary, 4032
        • Recruiting
        • University of Debrecen Clinical Center
        • Contact:
          • Robert Poka
  • Israel
      • Haifa, Israel, Rambam Medical Center
        • Recruiting
        • Rambam Medical Center
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center
      • Tel-Aviv, Israel, 6423906
        • Recruiting
        • Sourasky Medical Center
  • Italy
      • Catania, Italy, 95126
        • Recruiting
        • A.O. Cannizzaro
      • Forli, Italy, 47014
        • Recruiting
        • IRCCS Istituto Romangolo per lo Studio dei Tumori "Dino Amadori"
        • Contact:
          • Ugo De Giorgi
      • Genoa, Italy, 16132
        • Recruiting
        • Ospedale Policlinico San Martino
        • Contact:
          • Serafina Mammoliti
      • Lecco, Italy, 23900
        • Recruiting
        • ASST di Lecco-Ospedale Alessandro Manzoni
      • Lucca, Italy, 55100
        • Recruiting
        • Ospedale San Luca
        • Contact:
          • Editta Baldini
      • Milan, Italy, 20162
        • Recruiting
        • Osp. Niguarda
      • Parma, Italy, 43126
        • Recruiting
        • University Hospital Of Parma
      • Piacenza, Italy, 29121
        • Recruiting
        • Ospedale Guglielmo da Saliceto
        • Contact:
          • Rosa Porzio
      • Prato, Italy, 59100
        • Recruiting
        • Ospedale di Prato S. Stefano
      • Ravenna, Italy, 48121
        • Recruiting
        • Ospedale Santa Maria delle Croci
      • Rimini, Italy, 47923
        • Recruiting
        • "Azienda Unità Sanitaria Locale della Romagna - Hospital ""Infermi"" of Rimini Oncology Department"
        • Contact:
          • Marta Rosati
      • Rome, Italy, 00161
        • Recruiting
        • Policlinico Umberto
      • Varese, Italy, 21110
        • Recruiting
        • Ospedale Filippo Del Ponte
        • Contact:
          • Nicoletta Donadello
  • Lithuania
      • Kaunas, Lithuania, LT-45434
        • Recruiting
        • Health Sciences Kaunas Clinics
      • Vilnius, Lithuania, LT-08660
        • Recruiting
        • Nation Cancer Institute of Lithuania, Vilnius
  • Norway
      • Kristiansand, Norway, 4604
        • Recruiting
        • Southern Hospital Sorlandet
      • Oslo, Norway, 0379
        • Recruiting
        • Oslo University Hospital HF
      • Tromsø, Norway, 9038
        • Recruiting
        • Sykehusapotek Nord Tromsø
  • Poland
      • Bialystok, Poland, 15-027
        • Recruiting
        • Białostockie Centrum Onkologii
      • Gdansk, Poland, 80-210
        • Recruiting
        • Szpitale Pomorskie
        • Contact:
          • Joanna Pikiel
      • Gdańsk, Poland, 80-214
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne
      • Gliwice, Poland, 44-102
        • Recruiting
        • NIO-PIB Oddzial w Gliwicach
        • Contact:
          • Rafal Tarnawski
      • Kraków, Poland, 31-115
        • Recruiting
        • Centrum Badań klinicznych Jagiellońskie Centrum Innowacji
      • Olsztyn, Poland, 10-228
        • Recruiting
        • Siedleckie Centrum Onkologii
      • Poznan, Poland, 60-569
        • Recruiting
        • Uniwersytecki Szpital
      • Warsaw, Poland, 02-781
        • Recruiting
        • NIO-PIB Klinika Gine-Onk
      • Wroclaw, Poland, 53-413
        • Recruiting
        • Lower Silesian Oncology, Pulmonology and Hematology Center, Department of Oncological Gynecology
  • Romania
      • Bucharest, Romania, 012244
        • Recruiting
        • Bucharest CF2 Hospital
        • Contact:
          • Carmen Crihana
      • Constanta, Romania, 905900
        • Recruiting
        • Ovidius Clinical Hospital SRL
      • Craiova, Romania, 200094
        • Recruiting
        • Onco Clinic Consult S.A.
        • Contact:
          • Patricia Visan
      • Craiova, Romania, 200542
        • Recruiting
        • Oncology Center "Sf. Nectarie"
        • Contact:
          • Michael Schenker
      • Piteşti, Romania, 110283
        • Recruiting
        • Gral Medical S.R.L. - Oncofort Hospital
        • Contact:
          • Adela Chirila
      • Timisoara, Romania, 300239
        • Recruiting
        • SC Oncomed SRL
      • Timisoara, Romania, 300166
        • Recruiting
        • Oncocenter, Oncology Clinic SRL
        • Contact:
          • Roxana Scheusan
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • Institute of Oncology Ljubljana
        • Contact:
          • Erik Skof
      • Maribor, Slovenia, 2000
        • Recruiting
        • University Clinical Center Maribor
        • Contact:
          • Andrej Cokan
  • Spain
      • A Coruna, Spain, 15006
        • Recruiting
        • CHUAC (Hospital de Coruña)
        • Contact:
          • María Quindós Varela
      • Barcelona, Spain, 08003
        • Recruiting
        • Hospital del Mar
        • Contact:
          • Álvaro Taus García
      • Galdakao, Spain, 48960
        • Recruiting
        • Hospital Galdakao-Usansolo
        • Contact:
          • Josefa Ferreiro
      • Jaen, Spain, 23007
        • Recruiting
        • Hospital Universitario de Jaén
      • Jerez de la Frontera, Spain, 11407
        • Recruiting
        • H.G.U. Jerez de la Frontera
      • Las Palmas, Spain, 35016
        • Recruiting
        • Hospital U Insular de GC
      • Leon, Spain, 24008
        • Recruiting
        • Hospital de Leon
      • Santiago de Compostela, Spain, 15706
        • Recruiting
        • HCU Santiago de Compostela
        • Contact:
          • Juan Fernando Cueva Banuelos
      • Seville, Spain, 41014
        • Recruiting
        • Hospital Universitario de Valme
        • Contact:
          • Carlos Enrique Robles
  • Sweden
      • Linköping, Sweden, 581 85
        • Recruiting
        • Linköping University Hospital
      • Stockholm, Sweden, SE-171 76
        • Recruiting
        • Karolinska University Hospital
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Northside Hospital
      • Savannah, Georgia, United States, 31405
        • Recruiting
        • St. Joseph
    • Illinois
      • Hinsdale, Illinois, United States, 60521
        • Recruiting
        • Dr. Sudarshan K. Sharma, Ltd.
        • Contact:
          • Sudarshan Sharma
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Recruiting
        • Parkview Research Center
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University
    • Maryland
      • Silver Spring, Maryland, United States, 20904
        • Recruiting
        • Maryland Oncology Hematology, P.A.
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Minnesota Oncology Hematology, P.A.
    • Missouri
      • Saint Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University School of Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Recruiting
        • Women's Cancer Center of Nevada
        • Contact:
          • Nicola Spirtos
    • North Carolina
      • Pinehurst, North Carolina, United States, 28374
        • Recruiting
        • FirstHealth Carolinas
    • Ohio
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • OhioHealth Institute
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Recruiting
        • Oklahoma Cancer Specialists and Research Institute
        • Contact:
          • Michael Gold
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Oncology Associates of Oregon
      • Portland, Oregon, United States, 97227
        • Recruiting
        • Northwest Cancer Specialists
    • Texas
      • Austin, Texas, United States, 78745
        • Recruiting
        • Texas Oncology-Austin Central
        • Contact:
          • Helen Eshed
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • Texas Oncology-Fort Worth Cancer Center
        • Contact:
          • Noelle Cloven
      • San Antonio, Texas, United States, 78130
        • Recruiting
        • Texas Oncology-San Antonio Medical Center

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ECOG 0-1
  • Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT
  • Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1
  • Adequate hematologic, hepatic and renal function (within 14 days)

Exclusion Criteria:

  • Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation
  • Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days)
  • Indwelling surgical drains
  • Grade 2 or higher QTc prolongation
  • History of major organ transplant
  • History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 Arm 1
Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
Drug: Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
Other Names:
  • KRT-232
Experimental: Part 1 Arm 2
Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
Drug: Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
Other Names:
  • KRT-232
No Intervention: Part 1 Arm 3
Observational control ("watch and wait") on a 28-day cycle.
Experimental: Part 2 Arm A
Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
Drug: Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
Other Names:
  • KRT-232
Experimental: Part 2 Arm B
Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
Drug: Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
Other Names:
  • KRT-232
Placebo Comparator: Part 2 Arm C
Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
Drug: Navtemadlin Placebo
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth
Placebo Comparator: Part 2 Arm D
Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
Drug: Navtemadlin Placebo
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: To determine the navtemadlin Phase 3 dose
Time Frame: 12 months
Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1
12 months
Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo
Time Frame: 50 months
PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first
50 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment
Time Frame: 50 months
PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first
50 months
Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)
Time Frame: 50 months
TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first
50 months
Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
Will determine the Maximum observed concentration (Cmax)
1 day
Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
Will determine the area under the plasma concentration versus time curve (AUC)
1 day
Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
Will determine the time of maximum plasma concentration (Tmax)
1 day
Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR)
Time Frame: 50 months
Best response of complete response (CR), partial response (PR) or stable disease (SD) by IRC/investigator assessment among subjects with PR as best response from prior chemotherapy
50 months

Collaborators and Investigators

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

Sponsor

Kartos Therapeutics, Inc.

Collaborators

GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)

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)

July 17, 2023

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

March 7, 2023

First Submitted That Met QC Criteria

March 21, 2023

First Posted (Actual)

April 4, 2023

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-118
  • ENGOT en-21 (Other Identifier: ENGOT)
  • GOG-3089 (Other Identifier: GOG Foundation)

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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