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

Sponsor
Kartos Therapeutics, Inc. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05797831
Collaborator
(none)
268
Enrollment
7
Arms
48
Anticipated Duration (Months)

Study Details

Study Description

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
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Study Start Date :
Jul 1, 2023
Anticipated Primary Completion Date :
Aug 1, 2025
Anticipated Study Completion Date :
Jul 1, 2027

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: To determine the navtemadlin Phase 3 dose [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 [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 [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) [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 [1 day]

      Will determine the Maximum observed concentration (Cmax)

    4. Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [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 [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) [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Kartos Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kartos Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT05797831
    Other Study ID Numbers:
    • KRT-232-118
    First Posted:
    Apr 4, 2023
    Last Update Posted:
    Apr 4, 2023
    Last Verified:
    Mar 1, 2023
    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:
    Endometrial Neoplasms

    Study Results

    No Results Posted as of Apr 4, 2023