[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100607551":3},{"organization":4,"armGroups":7,"interventions":24,"overallOfficials":42,"centralContacts":43,"locations":42,"responsibleParty":49,"collaborators":42,"id":53,"slug":54,"hasResults":55,"nctId":56,"briefTitle":57,"officialTitle":58,"acronym":42,"eligibilityCriteria":59,"healthyVolunteers":55,"sex":60,"minAge":61,"maxAge":62,"enrollmentInfo":63,"targetDuration":42,"studyType":66,"phases":67,"briefSummary":70,"conditions":71,"keywords":73,"overallStatus":79,"whyStopped":42,"lastUpdateSubmitDate":80,"lastUpdatePostDateStruct":81,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":42},{"fullName":5,"class":6},"First Affiliated Hospital of Wenzhou Medical University","OTHER",[8,14,19],{"label":9,"type":10,"description":11,"interventionNames":12},"Arm 2: Fixed Delay Group","EXPERIMENTAL","Patients receive standard chemotherapy on Day 1 of each 21-day cycle. The PD-1 inhibitor is administered with a fixed delay, on Day 4 (3 days after chemotherapy). Combination treatment is given for 4 cycles, followed by PD-1 inhibitor maintenance until disease progression, unacceptable toxicity",[13],"Drug: Arm 2：Fixed Delay Group",{"label":15,"type":10,"description":16,"interventionNames":17},"Arm 1: Standard Synchronous Group","Patients receive standard chemotherapy and PD-1 inhibitor concurrently on Day 1 of each 21-day cycle. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression",[18],"Drug: Arm 1： Standard Synchronous Group",{"label":20,"type":10,"description":21,"interventionNames":22},"Arm 3: Individualized Delay Group","Patients receive chemotherapy on Day 1 of each 21-day cycle. From Day 2 to Day 5, peripheral blood immunodynamic markers (e.g., CD8⁺PD-1⁺ T cells, MDSCs, Tregs, cytokines) are monitored daily. The PD-1 inhibitor is administered at the optimal time when predefined immunodynamic criteria are met, or on Day 6 if criteria are not met. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression",[23],"Drug: Arm 3： Individualized Delay Group",[25,32,38],{"type":26,"name":27,"description":28,"armGroupLabels":29,"otherNames":30},"DRUG","Arm 1： Standard Synchronous Group","Arm 1: Concurrent PD-1 + Chemotherapy (Standard Synchronous Group) Participants in this group will receive PD-1 inhibitor and chemotherapy on the same day (D1) during each treatment cycle.",[15],[31],"Concurrent PD-1 + Chemotherapy",{"type":26,"name":33,"description":34,"armGroupLabels":35,"otherNames":36},"Arm 2：Fixed Delay Group","Fixed Delay Arm Delayed PD-1 + Chemo PD-1 inhibitor (e.g., Sintilimab\u002FKeytruda\u002FTislelizumab\u002FCamrelizumab\u002FToripalimab\u002FNivolumab\u002FAtezolizumab\u002FSugemalimab) Immune checkpoint inhibitor + Chemo (Day 3)",[9],[37],"PD-1 Delayed Administration on D3 (Fixed Delay Group) Participants in this group will receive chemotherapy on D1 and then receive the PD-1 inhibitor on D3 of each cycle.",{"type":26,"name":39,"description":40,"armGroupLabels":41,"otherNames":42},"Arm 3： Individualized Delay Group","Arm 3: Individualized PD-1 Timing Based on Immune Window Score (IWS) (Individualized Group) Participants in this group will receive chemotherapy on D1 and undergo daily immune monitoring (CD8⁺PD-1⁺ T cells, Treg, IFN-γ, NLR, ALC, CRP).\n\nBased on the immune window score (IWS):\n\nIf IWS ≥ 2, PD-1 inhibitor will be administered the same day. If IWS = 1-1.5, dosing may be delayed to D3-D5 depending on immune recovery. If IWS remains 0 by D5, PD-1 inhibitor will be administered on D6 as fallback.",[20],null,[44],{"name":45,"role":46,"phone":47,"phoneExt":42,"email":48},"xiaona xie","CONTACT","86+13758469563","xiexiaona@wmu.edu.cn",{"type":50,"investigatorFullName":51,"investigatorTitle":52,"investigatorAffiliation":5,"oldNameTitle":42,"oldOrganization":42},"PRINCIPAL_INVESTIGATOR","Liang bin","Clinical Investigator","100607551","phase-1-immunodynamics-guided-optimization-of-individualized-immunochemotherapy-in-advanced-driver-negative-nsclc-a-randomized-trial-100607551",false,"NCT07190027","Immunodynamics-Guided Optimization of Individualized Immunochemotherapy in Advanced Driver-Negative NSCLC: A Randomized Trial","Prospective Randomized Controlled Trial of Immunodynamics-Guided Optimization of Individualized Immunochemotherapy Infusion Timing in Driver Gene-Negative Advanced Non-Small Cell Lung Cancer","Inclusion Criteria:\n\nParticipants must meet all of the following criteria:\n\nVoluntarily agree to participate, sign the informed consent form (ICF), and be able to comply with the study procedures.\n\nAge ≥18 years and ≤75 years at enrollment, both male and female participants are eligible.\n\nHistologically or cytologically confirmed stage IV non-small cell lung cancer (NSCLC) based on the AJCC 8th edition; if mixed histology exists, classification must be based on the predominant histologic component. Presence of small-cell histology excludes eligibility.\n\nNegative for actionable driver mutations: no EGFR mutations, ALK rearrangements, or ROS1 fusions. For other targetable alterations (e.g., BRAF V600E, NTRK1\u002F2\u002F3 fusions, MET exon 14 skipping, RET rearrangements), patients are excluded if FDA- or NMPA-approved targeted therapies are available.\n\nNote: Genetic testing can be conducted locally or via a central laboratory. Pre-existing valid reports are acceptable.\n\nEstimated life expectancy ≥3 months. At least one measurable lesion per RECIST v1.1 confirmed by IRC; irradiated lesions are not considered measurable unless unequivocal progression is demonstrated.\n\nECOG performance status of 0 or 1. No prior systemic therapy for advanced\u002Fmetastatic NSCLC, except adjuvant or neoadjuvant chemotherapy if the last dose was ≥6 months before recurrence.\n\nAdequate organ and bone marrow function within 14 days prior to randomization:\n\nANC ≥ 1.5 × 10⁹\u002FL Platelets ≥ 100 × 10⁹\u002FL Hemoglobin ≥ 90 g\u002FL Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL\u002Fmin (Cockcroft-Gault formula) Total bilirubin ≤ 1.5 × ULN (≤3 × ULN for Gilbert's syndrome) AST\u002FALT ≤ 2.5 × ULN (≤5 × ULN if liver metastases) INR and APTT ≤ 1.5 × ULN unless on therapeutic anticoagulation LVEF ≥ 50% by echocardiography or MUGA Female patients of childbearing potential must test negative for pregnancy within 14 days before enrollment and agree to use effective contraception from ICF signing until 180 days after the last dose. Male participants must also agree to effective contraception during the same period.\n\nExclusion Criteria:\n\nParticipants meeting any of the following are excluded:\n\nPrior thoracic radiotherapy \\>30 Gy within 6 months before first dose. Palliative radiotherapy within 7 days before first dose. Requirement for concurrent anti-tumor therapy during the study. Uncontrolled or symptomatic pleural, pericardial, or peritoneal effusions requiring repeated drainage.\n\nBrainstem, leptomeningeal, spinal cord metastases, or cord compression.\n\nActive CNS metastases or carcinomatous meningitis. Treated, stable brain metastases are allowed if:\n\nClinically stable ≥2 weeks, No evidence of progression, Off corticosteroids ≥3 days prior to treatment initiation. Previous treatment with immune checkpoint inhibitors (PD-1\u002FPD-L1, CTLA-4, etc.), immune agonists, or cellular immunotherapies.\n\nUse of traditional Chinese medicines or immunomodulatory drugs with anti-cancer activity within 2 weeks before first dose.\n\nSystemic corticosteroids (\\>10 mg prednisone equivalent\u002Fday) or other immunosuppressants within 2 weeks prior to first dose.\n\nUncontrolled systemic infection, unexplained fever \\>38.5°C, or IV antibiotic use \\>7 days within 2 weeks prior to first dose.\n\nHistory of other malignancies within the past 5 years, except adequately treated cervical carcinoma in situ, basal\u002Fsquamous cell skin cancer, localized thyroid papillary carcinoma, prostate cancer in remission, or DCIS after curative surgery.\n\nActive or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.\n\nControlled hypothyroidism with hormone replacement is eligible. Vitiligo, alopecia, type 1 diabetes, resolved childhood asthma, or mild psoriasis without systemic therapy are allowed.\n\nClinically significant pulmonary diseases: e.g., steroid-requiring pneumonitis, drug-induced pneumonitis, or moderate-to-severe COPD.\n\nMajor surgery within 4 weeks prior to first dose or unresolved surgical wounds.\n\nSignificant cardiovascular diseases, including:\n\nMI, unstable angina, stroke, or TIA within 6 months Arterial thromboembolism within 6 months DVT, PE, or severe thrombosis within 3 months Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) Myocarditis or NYHA III-IV heart failure History of allogeneic HSCT or organ transplantation (except corneal).\n\n≥ Grade 2 peripheral neuropathy per CTCAE v5.0. Active tuberculosis or suspected TB not ruled out. Positive HIV antibody; active syphilis or untreated positive non-treponemal antibody; uncontrolled HBV\u002FHCV infection per protocol definition.\n\nLive vaccine administration within 30 days before first dose or planned during study.\n\nHistory of severe hypersensitivity to monoclonal antibodies, PD-1 agents, pemetrexed, carboplatin, or premedications.\n\nConcurrent participation in another interventional clinical trial or use of other investigational products\u002Fdevices within 4 weeks prior to first dose.\n\nHistory of drug\u002Falcohol abuse or uncontrolled psychiatric disorders interfering with compliance.\n\nAny other condition judged by the investigator as inappropriate for study participation.","ALL","18 Years","75 Years",{"count":64,"type":65},246,"ESTIMATED","INTERVENTIONAL",[68,69],"PHASE1","PHASE2","The goal of this clinical trial is to evaluate whether individualized sequencing of immunotherapy and chemotherapy based on immune dynamics can improve treatment outcomes in adults with advanced non-small cell lung cancer (NSCLC) without driver gene mutations. This study will also assess the safety and feasibility of different infusion strategies.\n\nThe main questions it aims to answer are:\n\nDoes optimizing the timing of PD-1 inhibitor infusion relative to chemotherapy improve the objective response rate (ORR)?\n\nDoes individualized infusion sequencing enhance progression-free survival (PFS) compared to standard or fixed-delay administration?\n\nWhat safety concerns or immune-related adverse events occur with different infusion timing strategies?\n\nResearchers will compare three treatment strategies:\n\nGroup A (Standard Concurrent Group): Immunotherapy and chemotherapy administered on the same day (D1).\n\nGroup B (Fixed Delay Group): Chemotherapy on D1, followed by PD-1 inhibitor infusion on Day 3.\n\nGroup C (Individualized Delay Group): Chemotherapy on D1, and PD-1 inhibitor infusion scheduled on D2-D6 based on daily immune monitoring.\n\nParticipants will:\n\nReceive a PD-1 inhibitor (e.g., sintilimab, pembrolizumab, camrelizumab) combined with platinum-based chemotherapy.\n\nAttend clinic visits for regular immune monitoring, imaging assessments, and safety checks during each treatment cycle.\n\nUndergo blood tests to evaluate immune biomarkers (e.g., CD8⁺PD-1⁺ T cells, MDSC, Treg、IFN-γ、NLR、ALC、CRP) to guide individualized treatment decisions.",[72],"Advanced Non-Small Cell Lung Cancer (NSCLC)",[74,75,76,77,78],"Non-Small Cell Lung Cancer (NSCLC)","Driver Gene-Negative NSCLC","Immunochemotherapy Sequencing","Individualized Infusion Timing","Immune Dynamics","NOT_YET_RECRUITING","2025-09-22",{"date":82,"type":83},"2025-09-24","ACTUAL",{"date":85,"type":65},"2025-11",{"date":87,"type":65},"2028-11",{"name":5,"class":6}]