[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"met-exon-14-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:met-exon-14-mutation":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,44,71],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":29,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100585947","phase-3-tepotinib-vs-standard-treatment-in-patients-with-advanced-met-exon-14-mutated-non-small-cell-lung-cancer-previously-treated-100585947",false,"NCT06908993","Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated","A Randomized Controlled Trial of Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer","COMET","Inclusion Criteria:\n\n1. Informed, written and signed consent:\n\n   * Patients must have signed and dated the written informed consent form approved by the ethics committee in accordance with the legal and institutional framework.\n   * It must have been signed before protocol-related procedures that are not part of normal patient management are performed. Patients should be willing and able to adhere to the schedule of visits, treatment and laboratory tests.\n2. Histologically proven advanced NSCLC.\n3. Presence of a METex14 mutation (based on local testing). Detection of METex14 mutation should be performed on a tissue sample if available. In case no tissue sample is available, detection of METex14 on a liquid biopsy is authorized. The sponsor should be consulted if there is any doubt about the nature of the mutation.\n4. Evidence of disease progression after at least one prior line of treatment including either a platinum-based chemotherapy or an anti-PD(L)1 agent or both.\n5. Has received no more than 2 prior lines of treatment.\n6. ECOG Performance Status 0-3.\n7. Brain metastases are allowed. If immediate local treatment is required, inclusion is possible once the latter is complete.\n8. Stage IIIB or IIIC non irradiable or stage IV (8th classification TNM, UICC 2015)\n9. Age ≥ 18 years.\n10. Adequate biological function:\n\n    * Creatinine clearance ≥ 30 ml\u002Fmin;\n    * Neutrophils ≥ 1500\u002Fmm3;\n    * Platelets ≥100,000\u002Fmm3;\n    * Haemoglobin ≥ 8 g\u002FdL;\n    * Liver enzymes \\\u003C 3x ULN except for patients with liver metastases (\\\u003C 5x ULN);\n    * Total bilirubin ≤ 1.5 x ULN except for patients with proven Gilbert's syndrome (≤ 5 x ULN) or patients with liver metastases (≤ 3.0 ULN).\n11. Protected adults may participate in the study if they are capable of making decisions regarding their medical treatment in accordance with the guardianship judgment.\n12. For women of childbearing potential (including women who have had a tubal ligation), serum pregnancy test must be performed and documented as negative within 14 days prior to C1D1.\n13. Women of childbearing potential must remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for at least 6 months after the last dose of study drugs. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries or uterus). Examples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method plus spermicide. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n14. Men with female partners of childbearing potential or pregnant female partners, must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n15. Patient covered by a national health insurance.\n\nExclusion Criteria:\n\n1. Prior treatment with a MET inhibitor (including crizotinib).\n2. Presence of another known driver oncogene alteration (including EGFR, HER2, KRAS, BRAF mutations or ALK, ROS1, RET fusions). In case of detection of any other driver alteration, inclusion should be discussed with the sponsor.\n3. ECOG Performance Status 4.\n4. Known hypersensitivity to tepotinib or its excipients.\n5. History of cancer within 3 years or active cancer except those with a negligible risk of metastasis or death, or those treated curatively. If a patient does not fulfil this criterion but the investigator considers that the benefit\u002Frisk balance is in favour of inclusion in the study, please contact IFCT.\n6. Inability to comply with study or follow-up procedures.\n7. Pregnant, lactating, or breastfeeding women.\n8. Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the patient at high risk from treatment complications.\n9. History of idiopathic pulmonary fibrosis or active pneumonitis on chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.","ALL","18 Years",{"count":20,"type":21},133,"ESTIMATED","INTERVENTIONAL",[24],"PHASE3","The hypothesize is that tepotinib is more effective than the investigator's choice of treatment in patients with MET-mutated NSCLC who have progressed after at least one first-line treatment.\n\nThe main benefit concerns patient access to tepotinib. There is currently no access to a new-generation MET TKI in France for METex14 patients, due to lack of comparative data. There are no phase III RCTs underway anywhere in the world. This study is the only opportunity, perhaps the last, to generate comparative data which, if positive, will enable the drug to be reimbursed. With this in mind, the methodology of this study was discussed with the HAS on several occasions beforehand, to ensure that it met their expectations. With a response rate of around 50% and a median progression-free survival of 11 months in previously-treated subjects based on clinical trials data, tepotinib is a key drug for METex14 NSCLC patients, who are generally elderly and frail, and for whom therapeutic options are limited.\n\nThe investigators expect to observe a benefit for patients treated with tepotinib compared to the control arm in terms of PFS, quality of life, objective response rate and duration of response. The overall survival benefit may be compromised by allowing patients in the control arm to cross over to tepotinib once they have progressed. However, the investigators have decided to maintain this crossover and consequently use PFS as the primary endpoint, as there is no clinical equipoise regarding the efficacy of tepotinib in METex14 NSCLC patients. The EMA has already approved tepotinib based on efficacy and safety data from clinical trials, and patients and investigators already consider this treatment as an important therapeutic option. Indeed, both ESMO and ASCO guidelines recommend the use of MET TKIs in these patients. In France, although neither tepotinib nor capmatinib are available, crizotinib, a multi-target TKI also active on MET, can be used off-label. If cross-over to tepotinib was not allowed in this trial, most patients would still benefit from cross-over to a MET TKI by receiving off-label crizotinib, which would in any case lead to a misinterpretation of the OS data. Therefore, the investigators believe it is preferable to control for cross-over and expose progressive patients in the control arm to tepotinib and use PFS as the primary endpoint.\n\nToxicity of MET TKIs is considered as manageable. In the VISION trial, of 313 patients treated with tepotinib (median age: 72 years), 109 (34.8%) experienced grade ≥3 treatment-related adverse events, leading to discontinuation in 46 patients (14.7%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Edema, the most common adverse event of clinical interest (AECI), was reported in 67.1% (grade ≥ 3, 11.2%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and\u002For treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild\u002Fmoderate: hypoalbuminemia, 23.6% (grade ≥ 3, 3.5%); creatinine increase, 22.0% (grade ≥ 3, 1.0%); nausea, 23.3% (grade ≥ 3, 0.6%), diarrhea, 22.4% (grade ≥ 3, 0.3%), decreased appetite (grade ≥ 3, 0.3%), and ALT increase, 14.1% (grade ≥ 3, 2.2%). GI AEs typically occurred early and resolved in the first weeks10,13.\n\nGiven the efficacy of tepotinib, the manageable safety profile, and the oral administration of tepotinib, the investigators anticipate that treatment with tepotinib will be associated with improved quality of life.\n\nTreatments offered in the control group correspond to standard treatments for advanced NSCLC in second line or beyond. In terms of prior lines of treatment, the eligibility criteria of the trial are aligned with the EMA label of tepotinib: \"indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to MET gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and\u002For platinum-based chemotherapy\". The investigators have not included platinum-based chemotherapy as a treatment option in the control arm, considering that patients who are eligible to platinum-based chemotherapy should have received this regimen in first-line, as per ESMO guidelines14. Given the low efficacy of immunotherapy in patients with oncogene addiction, it is unlikely that some patients would receive immunotherapy alone as first-line treatment. Thus, the absence of platinum-based chemotherapy as a treatment choice in the control arm seems reasonable and will reduce the heterogeneity of this arm.",[27,28],"Advanced Non Small Cell Lung Cancer","MET Exon 14 Mutation",[30,28,31],"Tepotinib","Non Small Cell Lung Cancer","RECRUITING","2025-12-09",{"date":35,"type":36},"2025-12-17","ACTUAL",{"date":33,"type":36},{"date":39,"type":21},"2028-07-15",{"name":41,"class":42},"Intergroupe Francophone de Cancerologie Thoracique","OTHER",29,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":22,"phases":52,"briefSummary":54,"conditions":55,"keywords":58,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":62,"lastUpdatePostDateStruct":63,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":4},"100604765","phase-2-bozitinib-combined-with-chemotherapy-as-radical-treatment-for-stage-iia-iiic-met-altered-non-small-cell-lung-cancer-100604765","NCT07153770","Bozitinib Combined With Chemotherapy as Radical Treatment for Stage IIA-IIIC MET-Altered Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Patients must meet all of the following inclusion criteria to participate in this study:\n* Signed informed consent.\n* Age ≥ 18 years.\n* Histologically or cytologically confirmed NSCLC adenocarcinoma, with -postoperative pathology confirming stage IIA-IIIC.\n* Willing to undergo curative resection, and assessed by a surgeon as operable with no surgical contraindications.\n* No prior systemic anti-tumor therapy.\n* Expected survival ≥ 6 months.\n* At least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.\n* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.\n* MET alteration confirmed by NGS gene testing, including the following types:\n\nMET exon 14 skipping mutation (NGS results from tissue or blood sample certified by CLIA or CAP).\n\n* MET primary amplification, NGS positive or FISH GCN ≥6 (results from tissue or blood sample certified by CLIA or CAP or FISH assay).\n* MET protein overexpression, immunohistochemistry showing ≥50% tumor cells with ++ or higher staining.\n* Adequate pulmonary function to tolerate surgery.\n* Adequate organ and bone marrow function, defined as:\n* Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL; platelets ≥ 100 × 10⁹\u002FL; hemoglobin ≥ 9.0 g\u002FdL.\n* Hepatic function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with HCC, liver metastases, or history\u002Fsuspected Gilbert syndrome (persistent or recurrent hyperbilirubinemia, mainly unconjugated, without evidence of hemolysis or liver lesions), TBIL ≤ 3 × ULN; for patients without HCC or liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.\n* Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL\u002Fmin; urine dipstick protein \\\u003C 2+.\n* Coagulation: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN.\n\nThyroid function: normal thyroid-stimulating hormone (TSH); if baseline TSH is outside the normal range, enrollment is allowed if total T3 (or FT3) and FT4 are within normal limits.\n\n* Cardiac enzymes: within normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator are acceptable).\n* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study drug (Cycle 1, Day 1). If urine pregnancy test cannot be confirmed negative, a serum pregnancy test is required. Non-childbearing females are defined as postmenopausal for at least 1 year, or surgically sterile (bilateral oophorectomy or hysterectomy).\n\nAll subjects with potential risk of pregnancy (male or female) must use highly effective contraception with a failure rate \\\u003C1% during treatment and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).\n\nExclusion Criteria:\n\n* Patients meeting any of the following criteria are not eligible for this study:\n\nPresence of EGFR, ALK, ROS1, or other actionable mutations excluding MET. Receipt of live attenuated vaccines within 4 weeks prior to enrollment or planned during the study period.\n\n* All participants must undergo brain imaging (MRI or contrast-enhanced CT) prior to enrollment to rule out brain metastases.\n* Major surgery (e.g., thoracic, abdominal, or pelvic) within 4 weeks prior to study treatment initiation, or ongoing recovery from surgical complications.\n\nDiagnosis of any malignancy other than NSCLC within 5 years prior to study treatment initiation (excluding completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ carcinoma, or completely resected papillary thyroid carcinoma).\n\n* Active, known, or suspected autoimmune disease.\n* Known history of primary immunodeficiency.\n* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.\n* Known hypersensitivity to the study drug bozitinib, platinum-based doublet chemotherapy, or any excipients.\n* Not fully recovered from any toxicity and\u002For complications caused by prior interventions (i.e., ≤ Grade 1 or returned to baseline, excluding fatigue or alopecia) prior to study treatment.\n* Untreated active hepatitis B infection (defined as HBsAg positive with detectable HBV-DNA above the upper limit of normal at the local laboratory).\n\nNote: Patients with hepatitis B meeting the following criteria may be enrolled:\n\nHBV viral load \\\u003C1000 copies\u002FmL (200 IU\u002FmL) prior to first dose; patients must receive antiviral therapy throughout chemotherapy to prevent viral reactivation.\n\nPatients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-) do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation.\n\n* Active hepatitis C infection (HCV antibody positive and HCV-RNA above the assay lower limit of detection).\n* Any history, condition, treatment, or laboratory abnormality that could interfere with study results, hinder full participation, or that the investigator considers a potential risk or inappropriate for enrollment.",{"count":51,"type":21},34,[53],"PHASE2","This study aim to evaluate the efficacy and safety of Bozitinib combined with chemotherapy as radical treatment for stage IIA-IIIC MET-altered non-small cell lung cancer",[56,28,57],"NSCLC","MET Activating Mutation",[56,59,60],"Bozitinib","Radical Treatment","NOT_YET_RECRUITING","2025-08-26",{"date":64,"type":36},"2025-09-04",{"date":66,"type":21},"2025-09-20",{"date":68,"type":21},"2028-09-20",{"name":70,"class":42},"Shanghai Pulmonary Hospital, Shanghai, China",{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":4,"eligibilityCriteria":77,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":78,"targetDuration":4,"studyType":22,"phases":80,"briefSummary":81,"conditions":82,"keywords":4,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":84,"lastUpdatePostDateStruct":85,"startDateStruct":87,"completionDateStruct":89,"leadSponsor":91,"locationsCount":93},"100520255","phase-2-neoadjuvant-and-adjuvant-targeted-treatment-in-nsclc-with-braf-v600-or-met-exon-14-mutations-100520255","NCT06054191","Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations","A Phase II, Two Parallel Group Study of Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations","Inclusion Criteria:\n\n* 18 years or older.\n* Histologically or cytologically diagnosed stage IB-IIIA and selected IIIB (T3N2, T4N2) NSCLC.\n* Presence of BRAF V600 mutation or METex14 skip mutation in tumor (by PCR or NGS) or blood (by NGS) (pre-treatment biopsy confirmed) in local or other Clinical Laboratory Improvement Amendments (CLIA)-certified lab.\n* Patients whose pre-surgical lesion is measurable, Eligible for surgical resection and scheduled for surgery within 2 weeks after the last does of neoadjuvant treatment.\n* ECOG performance-status score of 0 or 1.\n* No previous anticancer therapy.\n* Patients with stage II or higher non-small-cell lung cancer (NSCLC) and those with suspected brain metastases should have brain imaging (CT or MRI) prior to enrollment to exclude brain metastasis.\n* Could provide pretreatment tumor samples available for biomarker analysis. The subject should have good compliance, who would participate in the research voluntarily, and sign the informed consent.\n\nExclusion Criteria:\n\n* Patients with unresectable (regardless of stage) or metastatic disease (stage IV) or brain metastases.\n* Contain neuroendocrine carcinoma tumor histology.\n* Major surgery within 4 weeks before enrollment, or who have not recovered from side effects of related procedures.\n* History of current interstitial lung disease or pneumonitis.\n* Patients with conditions requiring systemic corticosteroids (\\>10 mg daily prednisone or equivalent) or immunosuppressive medication within 14 days of the first dose of study drug (Inhaled or topical steroids and adrenal-replacement steroids are allowed).\n* History of other malignancies within 5 years (excluding basal cell carcinoma of the skin or other carcinoma in situ that has been resected).\n* Pregnant or lactating women.\n* Those who are allergic to the research drug or its components.\n* Subjects who are deemed unable to comply with the study requirements or complete the study.\n* Those with acquired immunodeficiency syndrome, or any uncontrolled medical disorder, or insufficient function of bone marrow or other important organs.",{"count":79,"type":21},40,[53],"This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations.",[56,83,28],"BRAF V600 Mutation","2023-10-07",{"date":86,"type":36},"2023-10-10",{"date":88,"type":21},"2024-02-01",{"date":90,"type":21},"2027-03-01",{"name":92,"class":42},"Sun Yat-sen University",1]