[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"egfr-l858r\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:egfr-l858r":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,50],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":31,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":39,"lastUpdatePostDateStruct":40,"startDateStruct":43,"completionDateStruct":45,"leadSponsor":47,"locationsCount":4},"100628445","phase-1-an-open-label-single-arm-dose-escalation-phase-i-study-evaluating-the-safety-tolerability-and-preliminary-efficacy-of-edb-102-in-patients-with-egfr-l858r-mutant-third-generation-tki-resistant-advanced-non-small-cell-lung-cancer-with-liver-metastases-100628445",false,"NCT07461727","An Open-Label, Single-Arm, Dose-Escalation Phase I Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of EDB-102 in Patients With EGFR L858R-Mutant, Third-Generation TKI-Resistant Advanced Non-Small Cell Lung Cancer With Liver Metastases","Inclusion Criteria:\n\n1. Age ≥18 and ≤75 years, any sex.\n2. Histologically or cytologically confirmed, unresectable locally advanced or metastatic (stage IV) non-small cell lung cancer (NSCLC)\n3. Prior treatment with at least one third-generation EGFR-TKI (e.g., osimertinib) with radiologically confirmed disease progression according to RECIST 1.1 or intolerance, and no concomitant anticancer therapy during this period.\n4. Availability of tumor tissue obtained after progression on third-generation EGFR-TKI, with EGFR L858R mutation confirmed in the post-progression tumor tissue or blood sample by central laboratory- or study site-validated methods (e.g., WES or RNAseq).\n5. At least one measurable hepatic lesion per RECIST 1.1, confirmed by biopsy, with the EGFR L858R mutation verified in the lesion by central laboratory- or study site-validated methods (e.g., WES or RNAseq).\n6. ECOG performance status of 0 or 1.\n7. Adequate organ and bone marrow function: a) Hematologic: within 14 days prior to enrollment and without recent transfusion or growth factor therapy: ANC ≥1.5×10⁹\u002FL, Hb ≥90 g\u002FL, PLT ≥75×10⁹\u002FL, WBC \\>3.0×10⁹\u002FL. b) Hepatic: TBIL ≤1.5×ULN, ALT ≤5×ULN, AST ≤5×ULN. c) Renal: serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL\u002Fmin. d) Coagulation: PT ≤1.5×ULN, APTT ≤1.5×ULN, INR ≤1.5×ULN.\n8. Ability and willingness to provide written informed consent, comply with study procedures, and cooperate with study personnel.\n\nExclusion Criteria:\n\n1. Prior exposure to any gene-editing therapies (e.g., CRISPR, TALEN, ZFN)\n2. Receipt of chemotherapy, radiotherapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, or other anticancer agents within 4 weeks prior to the first dose of study drug. For oral fluoropyrimidines or small-molecule targeted agents, the washout period is 2 weeks or 5 half-lives of the drug, whichever is longer\n3. Receipt of any investigational, unapproved therapy within 4 weeks prior to the first dose of study drug.\n4. Presence of other known driver gene alterations conferring TKI resistance, excluding EGFR mutations, unless these occur as co-mutations, including: Bypass pathway activation: High-level MET amplification: detected by WES (gene copy number \\>5) or FISH (MET\u002FCEP7 ratio ≥2.0). High-level HER2 amplification: detected by ISH (gene copy number ≥6 per nucleus, HER2\u002FCEP17 ratio ≥2.0). Other acquired resistance driver mutations: Newly emerged confirmed resistance mutations, e.g., KRAS or BRAF-V600E. Activating mutations in PI3K\u002FAKT\u002FmTOR pathway genes (e.g., PIK3CA). Loss of primary EGFR mutation: absence of the original EGFR L858R mutation in post-resistance tumor tissue.\n5. Known allergy or adverse reaction to any lipid nanoparticle (LNP) components.\n6. Uncontrolled hypertension (systolic BP \\>150 mmHg and\u002For diastolic BP \\>100 mmHg despite regular antihypertensive therapy) or history of hypertensive crisis or hypertensive encephalopathy.\n7. Liver disease, including cirrhosis, hepatitis, or history of hepatitis B or C infection.\n8. Unstable angina or acute myocardial infarction, or history of these events within the past 6 months.\n9. History of malignancy within the past 5 years, except for treated basal cell carcinoma, cutaneous squamous cell carcinoma, cervical cancer, or gastrointestinal cancers.\n10. Pregnant, breastfeeding, positive pregnancy test, or unwillingness to use contraception in premenopausal women. Women are considered postmenopausal if amenorrheic for ≥2 years. Male patients unwilling to use contraception during the study are also excluded.\n11. Leptomeningeal, brainstem, or spinal metastases, or active CNS metastases with compression. Subjects with previously treated brain metastases may participate if clinically stable ≥4 weeks prior to first study drug administration and off corticosteroids for ≥14 days.\n12. Any condition deemed by the investigator to make the subject unsuitable for participation in the study.","ALL","18 Years","65 Years",{"count":19,"type":20},15,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of EDB-102 Injection in patients with advanced non-small cell lung cancer (NSCLC) who have liver metastases. The study specifically targets patients harboring the EGFR-L858R mutation who have disease progression after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs, e.g., osimertinib).\n\nEDB-102 is a novel in vivo gene-editing therapy. It consists of CRISPR-Cas9 mRNA and a single-guide RNA (sgRNA) encapsulated in lipid nanoparticles (LNPs). The drug is designed to specifically identify and disrupt the mutant EGFR-L858R gene in tumor cells, thereby inhibiting tumor growth. Due to the liver-targeting properties of the LNP carrier, this therapy is particularly aimed at patients with liver metastases.\n\nThis is a Phase I, open-label, dose-escalation study. Participants will receive a single intravenous (IV) infusion of EDB-102. The study will follow a \"3+3\" design to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). Participants will be monitored for adverse events, and tumor biopsies will be collected to assess the gene-editing efficiency of the drug.",[26,27,28,29,30],"Non-Small Cell Lung Cancer","Metastatic Non-small Cell Lung Cancer","Liver Metastases","EGFR Gene Mutation","EGFR L858R",[32,33,30,34,35,36,37],"EDB-102","CRISPR-Cas9","Lipid Nanoparticles (LNP)","In vivo Gene Editing","TKI Resistance","Osimertinib Resistance","NOT_YET_RECRUITING","2026-03-05",{"date":41,"type":42},"2026-03-10","ACTUAL",{"date":44,"type":20},"2026-02-10",{"date":46,"type":20},"2029-01-31",{"name":48,"class":49},"Cancer Institute and Hospital, Chinese Academy of Medical Sciences","OTHER",{"id":51,"slug":52,"hasResults":11,"nctId":53,"briefTitle":54,"officialTitle":54,"acronym":55,"eligibilityCriteria":56,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":21,"phases":59,"briefSummary":61,"conditions":62,"keywords":66,"overallStatus":70,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":80},"100520171","a-prospective-cohort-study-to-evaluate-molecular-prognostic-factors-and-resistance-mechanisms-to-osimertinib-in-adjuvant-treatment-of-completely-resected-pib-iiia-non-small-cell-lung-carcinoma-with-common-egfr-mutations-l858r-and-del19-100520171","NCT06053099","A Prospective Cohort Study to Evaluate Molecular pRognostic Factors and Resistance Mechanisms to Osimertinib in Adjuvant Treatment of Completely Resected pIB-IIIA Non-small Cell Lung Carcinoma With Common EGFR Mutations (L858R and Del19)","ROSIE","Inclusion Criteria:\n\n1. Signed Informed consent.\n2. Age ≥ 18 years.\n3. Pre-surgical disease evaluation including brain MRI\u002FCT-scan and total body PET-FDG CT-scan prior to surgery.\n4. Histologically complete anatomical resection (R0) of stage pIB-IIIA (pTNM 8th edition) NSCLC.\n5. Presence of a common EGFR mutation (Del19 or L858R).\n6. Archival tumour tissue FFPE blocks from surgery available for centrally molecular analyses.\n7. Patient eligible to receive osimertinib adjuvant therapy in a 3-year intent to treat decision; patients could receive if necessary adjuvant chemotherapy before starting osimertinib treatment.\n8. Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions.\n9. Patient followed in the institution on a regular basis (every 3 to 6 months) according to standard recommendations.\n10. Estimated life expectancy \\> 3 years.\n11. Woman patients who are of childbearing potential are eligible:\n\n    * They must have a negative pregnancy test before the first dose of osimertinib.\n    * They must agree to use effective methods of contraception throughout the course of treatment and should be maintained for 2 months after the end of treatment.\n12. Male subjects who are sexually active with a woman of childbearing potential are eligible if an efficacious contraception method should be used during the treatment and during the 4 months following the last dose.\n\nExclusion Criteria:\n\n1. History of cancer, except for the following situations:\n\n   Patients with history of cancer for more than 3 years are eligible if they have been treated and considered cured. Patients with history of in situ carcinoma of the cervix or non-melanoma skin carcinoma are eligible.\n2. Neoadjuvant anti-cancer treatment (osimertinib and\u002For chemotherapy or other anti-cancer treatment).\n3. Incompletely resected NSCLC (R1 or R2).\n4. Any medical condition that would, according to the investigator's judgment, prevent the patient's participation in the clinical study.\n5. Active infection (e.g. patients receiving treatment for infection) including hepatitis C virus (HCV) and human immunodeficiency virus (HIV), or active uncontrolled hepatitis B infection except for the situations described in APPENDIX I. Screening for chronic conditions is not required.",{"count":58,"type":20},300,[60],"NA","IFCT-2202 ROSIE study aims to incorporate a broad-panel centralized NGS testing at baseline in all patients with completely resected NSCLC with common EGFR mutation after confirmation of an optimal preoperative extension assessment and with a centralized review of the quality of the surgical excision. Furthermore, the IFCT-2202 ROSIE study also aims to study the molecular events associated with relapse on, or after osimertinib exposure, that should result in the opportunity to accede to optimal treatment in case of metastatic relapse.",[63,64,65,30],"Non Small Cell Lung Cancer","EGFR Activating Mutation","EGFR DEL19",[67,68,69],"IFCT","NSCLC","Adjuvant Osimertinib","RECRUITING","2024-03-06",{"date":73,"type":42},"2024-03-08",{"date":75,"type":42},"2024-01-22",{"date":77,"type":20},"2031-10",{"name":79,"class":49},"Intergroupe Francophone de Cancerologie Thoracique",36]