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

Study Overview
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Brief Summary
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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.

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

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: Navtemadlin
* Drug: Navtemadlin Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 months | 
| 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 | 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 | 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) | 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 | Will determine the Maximum observed concentration (Cmax) | 1 day | 
| Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin | 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 | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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navtemadlin