[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Qiming Wang\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":71},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,45],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":16,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":4},"100644564","phase-4-efficacy-and-safety-of-ensartinib-combined-with-anlotinib-in-lorlatinib-resistant-alk-positive-nsclc-100644564",false,"NCT07671560","Efficacy and Safety of Ensartinib Combined With Anlotinib in Lorlatinib-Resistant ALK-Positive NSCLC","Efficacy and Safety of Ensartinib Combined With Anlotinib in Lorlatinib-Resistant ALK-Positive Non-small Cell Lung Cancer(NSCLC): An Exploratory Analysis","Co-hort 1: Strict co-hort Inclusion criteria1：Histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer; Inclusion criteria2：Age ≥ 18 years at the time of signing the informed consent form; Inclusion criteria3：ALK-positive status confirmed by tissue samples or blood tests at each centre; Inclusion criteria4：History of resistance to lorlatinib treatment; prior use of ensartinib is not permitted; patients must have received a maximum of two other ALK-TKIs; prior receipt of ≤2 courses of chemotherapy is permitted; ECOG Performance Status (PS) score between 0 and 2, with no deterioration within 2 weeks prior to study entry;\n\nCo-hort 2 (Compassionate Use Cohort):\n\nInclusion criteria1： Resistance to lorlatinib treatment; Inclusion criteria2： No restrictions on prior use of ensartinib or the number of prior lines of other ALK-TKIs and chemotherapy; Inclusion criteria3：Subjects with concomitant leptomeningeal metastases may be enrolled. For patients with leptomeningeal metastases (LM), diagnosis must be based on the three criteria outlined in the EANO-ESMO guidelines: clinical presentation, cranial imaging, and cerebrospinal fluid cytology. Tissue samples must not be derived from tumour sites that have previously undergone radiotherapy; however, new lesions arising after local treatment may be included; Inclusion criteria4：ECOG performance status of 0-4; Inclusion criteria5： Adequate organ system function, as determined by the investigator; Inclusion criteria6：All other inclusion criteria are consistent with items 1, 2 and 3 of Cohort 1.\n\nExclusion criteria1：Concurrent malignant tumours. Exclusion criteria2：Patients with leptomeningeal metastases (LM) who are unable to undergo contrast-enhanced MRI.\n\nExclusion criteria3：Patients who have undergone surgery within 4 weeks prior to treatment with the study drug, except for minor procedures deemed by the investigator not to preclude participation in the trial; or patients scheduled to undergo major surgery during the study period.\n\nExclusion criteria4：Patients who have experienced a marked deterioration in symptoms or signs within 2 weeks prior to screening and are deemed by the investigator to be unsuitable for participation in the trial.",true,"ALL","18 Years",{"count":20,"type":21},80,"ESTIMATED","INTERVENTIONAL",[24],"PHASE4","ALK TKIs, particularly second- and third-generation ALK TKIs, have significantly improved progression-free survival (PFS) in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). However, patients continue to face challenges related to drug resistance and disease progression; in the CROWN study, 40% of patients still experienced disease progression within five years. There are currently no standard treatment recommendations for this patient population. This study retrospectively evaluated the efficacy and safety of ensartinib combined with anlotinib as a second-line treatment in patients who had developed resistance to lorlatinib. The inclusion criteria for data collection were patients aged ≥18 years with histologically confirmed stage IIIB-IV ALK-positive NSCLC who had developed resistance to lorlatinib; prior to lorlatinib treatment, patients could have received up to two other ALK-TKIs, excluding ensartinib.",[27],"ALK-positive, Locally Advanced or Metastatic (TNM Stage IIIB-IV) Non-small Cell Lung Cancer That Has Developed Resistance to Prior Treatment With Lorlatinib",[29,30,31,32],"Lorlatinib resistance","Ensartinib","Anlotinib","ALK-positive non-small cell lung cancer","NOT_YET_RECRUITING","2026-06-23",{"date":36,"type":37},"2026-06-26","ACTUAL",{"date":39,"type":21},"2026-07-01",{"date":41,"type":21},"2028-12-31",{"name":43,"class":44},"Qiming Wang","OTHER_GOV",{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":22,"phases":55,"briefSummary":57,"conditions":58,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":4},"100590744","phase-2-high-dose-firmonertinib-combined-with-bevacizumab-and-intrathecal-pemetrexed-in-the-treatment-of-egfr-mutated-non-small-cell-lung-cancer-with-leptomeningeal-metastasis-100590744","NCT06971406","High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis","A Multicenter, Prospective Phase II Clinical Study of High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis","FLAME-1","Inclusion Criteria:\n\n1. Have obtained written informed consent from the patient or his or her legal representative.\n2. Age ≥18 years, male or female.\n3. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).\n4. EGFR mutations confirmed by genetic testing (EGFR Ex19del\u002FL858R\u002FEx20ins\u002FPACC\u002FL861Q).\n5. Leptomeningeal metastasis diagnosed by comprehensive clinical assessment according to \"EANO-ESMO\" diagnostic criteria, including symptom evaluation, imaging assessment, and\u002For cerebrospinal fluid (CSF) cytopathological evaluation.\n6. Both treatment-naïve leptomeningeal metastasis patients and those who progressed after standard antitumor therapies in clinical practice are eligible. ≤3 prior lines of therapy allowed (patients with \\>3 prior lines may enroll in the real-world study cohort).\n7. ECOG PS 0-2 (patients with ECOG PS \\>2 may enroll in the real-world study cohort).\n8. Prior radiotherapy or surgical treatment targeting the central nervous system (CNS) is permitted.\n9. Patients with CNS symptoms\u002Fsigns are allowed if these manifestations are not life-threatening.\n10. Patients previously treated with standard-dose third-generation EGFR TKIs, pemetrexed intravenous infusion, or bevacizumab are permitted.\n11. Adequate organ function:\n\n    Absolute neutrophil count (ANC) ≥1.5×10\\^9\u002FL, platelets ≥75×10\\^9\u002FL, hemoglobin ≥80g\u002FL Total bilirubin ≤1.5×ULN, AST\u002FALT ≤2.5×ULN (≤3×ULN for bilirubin and ≤5×ULN for AST\u002FALT in cases with liver metastasis) Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL\u002Fmin (calculated by Cockcroft-Gault formula).\n12. Sexually active males or females of childbearing potential must use highly effective contraception (e.g., oral contraceptives, IUD, abstinence, or barrier methods with spermicide) during the trial and for 12 months after treatment completion.\n\nExclusion Criteria:\n\n1. Diagnosis of other malignancies within the past 5 years or history of other malignancies (except adequately controlled basal cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast).\n2. Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.\n3. Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.\n4. Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.\n5. Evidence of any severe or uncontrolled systemic diseases, including uncontrolled hypertension, diabetes, active bleeding, or active infections (e.g., hepatitis B\u002FC, HIV), which in the investigator's judgment may jeopardize patient participation or protocol compliance.\n6. History of steroid-requiring radiation pneumonitis or any evidence of active interstitial lung disease.\n7. Clinically significant cardiac arrhythmias (e.g., QTc interval \\>500 ms) or heart failure (left ventricular ejection fraction \\\u003C50%).\n8. Pregnant or lactating women.\n9. Patients currently participating in or having received investigational drug therapy within 2 weeks prior to enrollment.\n10. Other severe acute\u002Fchronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase study-related risks, interfere with result interpretation, or compromise the patient's ability to complete the study or adhere to protocol requirements.",{"count":54,"type":21},100,[56],"PHASE2","Primary Objective:\n\nTo evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del\u002FL858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS).\n\nSecondary Objectives:\n\n1. To assess the efficacy of this regimen in EGFR Ex20ins\u002FPACC\u002FL861Q-mutated NSCLC with LM.\n2. To further evaluate therapeutic outcomes across cohorts, including:\n\n   * Time to Treatment Failure (TTF)\n   * Leptomeningeal Objective Response Rate (ORR-LM)\n   * Clinical Response Rate\n3. To analyze the impact of this regimen on \\*quality of life\\* using standardized metrics:\n\n   * EORTC QLQ-C30\n   * EORTC QLQ-LC13\n4. To assess safety profiles across cohorts, focusing on:\n\n   * Incidence and severity of adverse events (AEs) graded per \\*CTCAE v5.0\\*\n   * Frequency of treatment-related toxicities\n\nExploratory Objectives:\n\nTo investigate correlations between dynamic changes in:\n\n* Plasma-derived circulating tumor DNA (ctDNA)\n* Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.",[59,60,61,62],"Non Small Cell Lung Cancer","EGFR Mutation","Leptomeningeal Metastases","Targeted Therapy","2025-05-06",{"date":65,"type":37},"2025-05-14",{"date":67,"type":21},"2025-05-15",{"date":69,"type":21},"2027-06-01",{"name":43,"class":44},""]