Ignite Creation Date:
2025-12-25 @ 12:33 AM
Ignite Modification Date:
2025-12-25 @ 10:41 PM
Study NCT ID:
NCT06045767
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-03
First Post:
2023-09-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-small Lung Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'D007267', 'term': 'Injections'}, {'id': 'D016190', 'term': 'Carboplatin'}, {'id': 'D000068437', 'term': 'Pemetrexed'}], 'ancestors': [{'id': 'D004333', 'term': 'Drug Administration Routes'}, {'id': 'D004358', 'term': 'Drug Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D056831', 'term': 'Coordination Complexes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D006147', 'term': 'Guanine'}, {'id': 'D007042', 'term': 'Hypoxanthines'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D005971', 'term': 'Glutamates'}, {'id': 'D024342', 'term': 'Amino Acids, Acidic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000600', 'term': 'Amino Acids, Dicarboxylic'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2024-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-05', 'completionDateStruct': {'date': '2029-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-05-30', 'studyFirstSubmitDate': '2023-09-13', 'studyFirstSubmitQcDate': '2023-09-13', 'lastUpdatePostDateStruct': {'date': '2024-06-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-09-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Objective Response Rate (ORR) per RECIST 1.1 - correlated to TCR repertoire data, such as clonality/diversity.', 'timeFrame': '5 years', 'description': 'ORR defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by the investigator.\n\nBy integrating serial TCR repertoire sequencing (Rep-seq) of NSCLC patients treated with pembrolizumab and platinum-based chemotherapy regimens we aim to capture the temporal clonality and diversity dynamics with the disease response.'}], 'secondaryOutcomes': [{'measure': 'Objective Response Rate (ORR) correlated with circulating tumor DNA (ctDNA), by measurement of variant allele frequency (VAF).', 'timeFrame': '5 years', 'description': 'To capture the VAF in ctDNA, and correlate it with response to therapy evaluated by ORR per RECIST 1.1. We will capture its dynamics throughout blood samples collected longitudinally (pre-and during treatment).'}]}, 'oversightModule': {'isUsExport': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['T-cell repertoire', 'ctDNA'], 'conditions': ['Non-small Cell Lung Cancer Metastatic']}, 'descriptionModule': {'briefSummary': 'This is a single site, non-randomized trial for the assessment of intravenous (IV) pembrolizumab (also known as MK-3475) combined with pemetrexed/platinum-based chemotherapy in subjects with advanced or metastatic non-squamous non-small lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease and in whom directed therapy is not indicated. Approximately 30 subjects will be enrolled in this trial to examine the clonality and diversity dynamics matched with disease response evaluated by RECIST 1.1.', 'detailedDescription': "Subjects will receive pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin), as indicated below:\n\nPembrolizumab 200 mg + pemetrexed 500 mg/m2 (with vitamin supplementation) + cisplatin 75 mg/m2 OR carboplatin AUC 5, all on Day 1 every 3 weeks (Q3W) for 4 cycles followed by pembrolizumab 200 mg + pemetrexed 500 mg/m2 Q3W until progression.\n\nTreatment with pembrolizumab and pemetrexed will continue until 35 trial treatments have been administered, documented disease progression or unacceptable adverse event(s).\n\nPatients will be stratified according to clinical and histopathological parameters: 1. PD-L1 status (PD-L1 \\>/= 1 or \\<1) 2. Age \\< 65 vs =\\> 65 3. Smoking history yes vs no 4. Platinum chemotherapy: cisplatin vs. carboplatin 5. Immune-related adverse events (irAEs).\n\nTCR repertoire clonality and diversity will serve as an assessment measure for treatment response, along with PET/CT-scans, tumor exomal profile and ctDNA dynamics."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participant (or legally acceptable representative if applicable) provides written informed consent for the trial.\n* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.\n* Archival tumor tissue sample or newly obtained \\[core, incisional or excisional\\] biopsy of a tumor lesion not previously irradiated has been provided.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n* Adequate organ function.\n\nExclusion Criteria:\n\n* Pregnancy or breastfeeding\n* Aberration in a known targetable molecular driver.\n* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.\n* Received prior systemic anti-cancer therapy for metastatic disease.\n* Received prior radiotherapy within 2 weeks of start of study intervention.\n* Major surgery within 14 days.\n* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.\n* Known additional malignancy that is progressing or has required active treatment within the past 3 years.\n* Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated or asymptomatic brain metastases may participate provided they are radiologically stable.'}, 'identificationModule': {'nctId': 'NCT06045767', 'briefTitle': 'T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-small Lung Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Tel Aviv Medical Center'}, 'officialTitle': 'T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-small Lung Cancer', 'orgStudyIdInfo': {'id': '0222-24 TLV'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Pembrolizumab + Carboplatin+ Pemetrexed', 'interventionNames': ['Drug: Pembrolizumab 50 MG Injection [Keytruda]']}], 'interventions': [{'name': 'Pembrolizumab 50 MG Injection [Keytruda]', 'type': 'DRUG', 'otherNames': ['Carboplatin', 'Pemetrexed'], 'description': 'Chemo-immunotherapy combination', 'armGroupLabels': ['Pembrolizumab + Carboplatin+ Pemetrexed']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Ari Raphael, M.D', 'role': 'CONTACT', 'email': 'arir@tlvmc.gov.il', 'phone': '+972-3-6973082'}], 'overallOfficials': [{'name': 'Ari Raphael, M.D', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Tel-Aviv University school of medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ari Raphael', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bar-Ilan University, Israel', 'class': 'OTHER'}, {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Head Oncology Day-care unit', 'investigatorFullName': 'Ari Raphael', 'investigatorAffiliation': 'Tel Aviv Medical Center'}}}}