Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
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ClinicalTrials.gov Identifier: NCT05797831 |
Recruitment Status :
Recruiting
First Posted : April 4, 2023
Last Update Posted : April 16, 2024
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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 |
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.
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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.
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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.
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Experimental: Part 2 Arm A
Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
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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.
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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.
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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.
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Drug: Navtemadlin Placebo
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth |
- 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
- 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
- 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
- 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
- Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]Will determine the Maximum observed concentration (Cmax)
- 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)
- 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)
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
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)
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
Contact: John Mei | 650-542-0136 | jmei@kartosthera.com |
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: | April 16, 2024 |
Last Verified: | April 2024 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
navtemadlin |
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 |