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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05797831
Recruitment Status : Recruiting
First Posted : April 4, 2023
Last Update Posted : December 1, 2023
Sponsor:
Collaborators:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Navtemadlin Drug: Navtemadlin Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 268 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy
Actual Study Start Date : July 17, 2023
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : July 2027

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 Name: 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 Name: 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 Name: 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 Name: 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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
    Will determine the Maximum observed concentration (Cmax)

  4. 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)

  5. 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)

  6. 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



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

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)

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): NCT05797831


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

Locations
Show Show 49 study locations
Sponsors and Collaborators
Kartos Therapeutics, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05797831    
Other Study ID Numbers: KRT-232-118
ENGOT en-21 ( Other Identifier: ENGOT )
GOG-3089 ( Other Identifier: GOG Foundation )
First Posted: April 4, 2023    Key Record Dates
Last Update Posted: December 1, 2023
Last Verified: November 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kartos Therapeutics, Inc.:
navtemadlin
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases