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

Primary Purpose

Endometrial Cancer

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Navtemadlin

Navtemadlin Placebo

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring navtemadlin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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)

Sites / Locations

Dr. Sudarshan K. Sharma, Ltd.Recruiting
Oklahoma Cancer Specialists and Research InstituteRecruiting
University Hospital Graz, Department of Gynecology and ObstetricsRecruiting
LTD High Technology hospital MedcenterRecruiting
American Hospital Network LLCRecruiting
Caucasus Medical CentreRecruiting
Onco Clinic Consult S.A.Recruiting
Gral Medical S.R.L. - Oncofort HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

No Intervention

Experimental

Placebo Comparator

Arm Label

Part 1 Arm 1

Part 1 Arm 2

Part 1 Arm 3

Part 2 Arm A

Part 2 Arm B

Part 2 Arm C

Part 2 Arm D

Arm Description

Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Observational control ("watch and wait") on a 28-day cycle.

Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Outcomes

Primary Outcome Measures

Part 1: To determine the navtemadlin Phase 3 dose

Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1

Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo

PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first

Secondary Outcome Measures

Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment

PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first

Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)

TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first

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

Will determine the Maximum observed concentration (Cmax)

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

Will determine the area under the plasma concentration versus time curve (AUC)

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

Will determine the time of maximum plasma concentration (Tmax)

Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR)

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

Full Information

NCT ID

NCT05797831

First Posted

March 7, 2023

Last Updated

September 6, 2023

Sponsor

Kartos Therapeutics, Inc.

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05797831

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 17, 2023 (Actual)

Primary Completion Date

August 2025 (Anticipated)

Study Completion Date

July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kartos Therapeutics, Inc.

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometrial Cancer

Keywords

navtemadlin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

268 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1 Arm 1

Arm Type

Experimental

Arm Description

Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Arm Title

Part 1 Arm 2

Arm Type

Experimental

Arm Description

Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Arm Title

Part 1 Arm 3

Arm Type

No Intervention

Arm Description

Observational control ("watch and wait") on a 28-day cycle.

Arm Title

Part 2 Arm A

Arm Type

Experimental

Arm Description

Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Arm Title

Part 2 Arm B

Arm Type

Experimental

Arm Description

Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Arm Title

Part 2 Arm C

Arm Type

Placebo Comparator

Arm Description

Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Arm Title

Part 2 Arm D

Arm Type

Placebo Comparator

Arm Description

Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Intervention Type

Drug

Intervention Name(s)

Navtemadlin

Other Intervention Name(s)

KRT-232

Intervention Description

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth

Intervention Type

Drug

Intervention Name(s)

Navtemadlin Placebo

Intervention Description

Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth

Primary Outcome Measure Information:

Title

Part 1: To determine the navtemadlin Phase 3 dose

Description

Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1

Time Frame

12 months

Title

Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo

Description

PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first

Time Frame

50 months

Secondary Outcome Measure Information:

Title

Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment

Description

PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first

Time Frame

50 months

Title

Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)

Description

TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first

Time Frame

50 months

Title

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

Description

Will determine the Maximum observed concentration (Cmax)

Time Frame

1 day

Title

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

Description

Will determine the area under the plasma concentration versus time curve (AUC)

Time Frame

1 day

Title

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

Description

Will determine the time of maximum plasma concentration (Tmax)

Time Frame

1 day

Title

Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR)

Description

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

Time Frame

50 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

John Mei

Phone

650-542-0136

jmei@kartosthera.com

Facility Information:

Facility Name

Dr. Sudarshan K. Sharma, Ltd.

City

Hinsdale

State/Province

Illinois

ZIP/Postal Code

60521

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sudarshan Sharma

Facility Name

Oklahoma Cancer Specialists and Research Institute

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74146

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Gold

Facility Name

University Hospital Graz, Department of Gynecology and Obstetrics

City

Graz

ZIP/Postal Code

8036

Country

Austria

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Edgar Petru

Facility Name

LTD High Technology hospital Medcenter

City

Batumi

ZIP/Postal Code

6000

Country

Georgia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tamta Makharadze

Facility Name

American Hospital Network LLC

City

Tbilisi

ZIP/Postal Code

0102

Country

Georgia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zaza Tsitsishvili

Facility Name

Caucasus Medical Centre

City

Tbilisi

ZIP/Postal Code

0186

Country

Georgia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lika Katselashvili

Facility Name

Onco Clinic Consult S.A.

City

Craiova

ZIP/Postal Code

200094

Country

Romania

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Patricia Visan

Facility Name

Gral Medical S.R.L. - Oncofort Hospital

City

Piteşti

ZIP/Postal Code

110283

Country

Romania

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Adela Chirila

12. IPD Sharing Statement

Learn more about this trial

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

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