- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05705466
Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer
A Two-Part, Phase 1b/2, Multicenter, Open-Label, Dose Escalation and Double-Blind, Randomized, Placebo-Controlled, Dose Expansion Study of the Safety, Efficacy and Pharmacokinetics of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Subjects With Locally Advanced and Metastatic Non-Small Cell Lung Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a 2 part, phase 1b/2, maintenance study for patients who have achieved a partial response (PR) or complete response (CR) after completion of up to 4 cycles of a combination platinum-based chemotherapy plus CPI regimen.
Phase 1b is a 3+3 dose escalation design that will be used to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of navtemadlin in combination with pembrolizumab. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.
Phase 2 will evaluate the efficacy and safety of the RP2D of navtemadlin plus pembrolizumab compared to navtemadlin placebo plus pembrolizumab. Each Arm will have approximately 40 subjects enrolled for a total of approximately 80 subjects. Eligible subjects will be randomized 1:1. This part of the study has a randomized, controlled, double-blind design. A stratified, permuted-block randomization scheme will be used for treatment allocation.
Study Type
Phase
- Phase 2
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- ECOG 0-1
- Histologically or cytologically confirmed diagnosis of NSCLC documented as TP53WT
- Locally advanced or metastatic disease; must have completed up to 4 cycles of platinum-based chemo plus CPI and achieved a CR or PR per RECIST V1.1
- Adequate hematologic, hepatic and renal function (within 14 days)
Exclusion Criteria:
- Symptomatic or uncontrolled central nervous system (CNS) metastases
- Prior treatment with a MDM2 inhibitor
- Grade 2 or higher QTc prolongation (>480 msec per NCI-CTCAE criteria version 5.0)
- History of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 24 weeks
- History of major organ transplant
- Active pneumonitis or known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis
- Prior radiotherapy, cytoreductive therapy, cytokine therapy or any investigational therapy within 28 days
- Medical condition, serious intercurrent illness, psychiatric condition or other circumstance that, in the Investigator's judgment could jeopardize the subject's safety, or that could interfere with study objectives
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Navtemadlin in combination with pembrolizumab
Navtemadlin will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. |
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.
Other Names:
Pembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously
Other Names:
|
Placebo Comparator: Navtemadlin placebo in combination with pembrolizumab
Navtemadlin placebo will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. |
Pembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously
Other Names:
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b- To determine the recommended Phase 2 dose (RP2D)
Time Frame: 21 days
|
The Safety Review Committee will determine the RP2D based on safety data of the combination of navtemadlin and pembrolizumab.
|
21 days
|
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
Time Frame: 64 Months
|
PFS is defined as the time from randomization date to disease progression (assessed by the Independent Review Committee [IRC] per RECIST v1.1) or death, whichever occurs first
|
64 Months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
|
Will determine the Maximum observed concentration (Cmax) on Cycle 1 Day 1
|
1 day
|
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
|
Will determine the area under the plasma concentration versus time curve (AUC) on Cycle 1 Day 1
|
1 day
|
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time Frame: 1 day
|
Will determine the time of maximum plasma concentration (Tmax) on Cycle 1 Day 1
|
1 day
|
Phase 1b- To assess the treatment effect on progression-free survival (PFS)
Time Frame: 64 Months
|
PFS is defined as the time from first dose date to disease progression (assessed by the IRC and Investigator per RECIST v1.1) or death, whichever occurs first
|
64 Months
|
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
Time Frame: 64 Months
|
PFS is defined as the time from randomization date to disease progression (assessed by the Investigator per RECIST v1.1) or death, whichever occurs first
|
64 Months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- KRT-232-119
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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