Ignite Creation Date:
2025-12-24 @ 4:23 PM
Ignite Modification Date:
2025-12-31 @ 9:11 PM
Study NCT ID:
NCT05705466
Status:
WITHDRAWN
Last Update Posted:
2024-03-22
First Post:
2023-01-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}], 'ancestors': [{'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000723723', 'term': 'navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid'}, {'id': 'C582435', 'term': 'pembrolizumab'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Sponsor Decision', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2023-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2027-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-03-21', 'studyFirstSubmitDate': '2023-01-17', 'studyFirstSubmitQcDate': '2023-01-27', 'lastUpdatePostDateStruct': {'date': '2024-03-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-01-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Phase 1b- To determine the recommended Phase 2 dose (RP2D)', 'timeFrame': '21 days', 'description': 'The Safety Review Committee will determine the RP2D based on safety data of the combination of navtemadlin and pembrolizumab.'}, {'measure': '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.', 'timeFrame': '64 Months', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin', 'timeFrame': '1 day', 'description': 'Will determine the Maximum observed concentration (Cmax) on Cycle 1 Day 1'}, {'measure': 'Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin', 'timeFrame': '1 day', 'description': 'Will determine the area under the plasma concentration versus time curve (AUC) on Cycle 1 Day 1'}, {'measure': 'Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin', 'timeFrame': '1 day', 'description': 'Will determine the time of maximum plasma concentration (Tmax) on Cycle 1 Day 1'}, {'measure': 'Phase 1b- To assess the treatment effect on progression-free survival (PFS)', 'timeFrame': '64 Months', 'description': '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'}, {'measure': '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.', 'timeFrame': '64 Months', 'description': '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'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Navtemadlin'], 'conditions': ['Non Small Cell Lung Cancer']}, 'descriptionModule': {'briefSummary': 'This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer.', 'detailedDescription': '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.\n\nPhase 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.\n\nPhase 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* ECOG 0-1\n* Histologically or cytologically confirmed diagnosis of NSCLC documented as TP53WT\n* 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\n* Adequate hematologic, hepatic and renal function (within 14 days)\n\nExclusion Criteria:\n\n* Symptomatic or uncontrolled central nervous system (CNS) metastases\n* Prior treatment with a MDM2 inhibitor\n* Grade 2 or higher QTc prolongation (\\>480 msec per NCI-CTCAE criteria version 5.0)\n* History of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 24 weeks\n* History of major organ transplant\n* Active pneumonitis or known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis\n* Prior radiotherapy, cytoreductive therapy, cytokine therapy or any investigational therapy within 28 days\n* 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"}, 'identificationModule': {'nctId': 'NCT05705466', 'briefTitle': 'Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer', 'organization': {'class': 'INDUSTRY', 'fullName': 'Kartos Therapeutics, Inc.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'KRT-232-119'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Navtemadlin in combination with pembrolizumab', 'description': 'Navtemadlin will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.\n\nPembrolizumab will be administered intravenously on Day 1 of a 21-day cycle.', 'interventionNames': ['Drug: Navtemadlin', 'Drug: Pembrolizumab']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Navtemadlin placebo in combination with pembrolizumab', 'description': 'Navtemadlin placebo will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.\n\nPembrolizumab will be administered intravenously on Day 1 of a 21-day cycle.', 'interventionNames': ['Drug: Navtemadlin Placebo', 'Drug: Pembrolizumab']}], 'interventions': [{'name': 'Navtemadlin', 'type': 'DRUG', 'otherNames': ['KRT-232'], 'description': 'Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.', 'armGroupLabels': ['Navtemadlin in combination with pembrolizumab']}, {'name': 'Navtemadlin Placebo', 'type': 'DRUG', 'description': 'Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth.', 'armGroupLabels': ['Navtemadlin placebo in combination with pembrolizumab']}, {'name': 'Pembrolizumab', 'type': 'DRUG', 'otherNames': ['Keytruda'], 'description': 'Pembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously', 'armGroupLabels': ['Navtemadlin in combination with pembrolizumab', 'Navtemadlin placebo in combination with pembrolizumab']}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kartos Therapeutics, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}