[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"egfr-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:egfr-mutation":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,43,71,95],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100446879","phase-1-first-in-human-study-of-bay2927088-in-participants-who-have-advanced-non-small-cell-lung-cancer-nsclc-with-mutations-in-the-genes-of-epidermal-growth-factor-receptor-egfr-andor-human-epidermal-growth-factor-receptor-2-her2-100446879",false,"NCT05099172","First in Human Study of BAY2927088 in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Epidermal Growth Factor Receptor (EGFR) and\u002For Human Epidermal Growth Factor Receptor 2 (HER2)","An Open Label, First-in-human Study of BAY 2927088 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) Harboring an EGFR and\u002For HER2 Mutation","Inclusion Criteria:\n\n* Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).\n* Documented disease progression after treatment with at least one prior systemic therapy for advanced disease. Participants who do not have standard of care access due to any reason, are intolerant to, or are not eligible for standard treatments, may also be eligible.\n\nNote: Except for participants eligible for Group F and Group H (Expansion or Extension) who should have received no prior systemic treatment for locally advanced or metastatic disease.\n\n* Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant.\n* Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy during the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments (or, for participants in Expansion Group G and Group H, for RANO-BM tumor assessments). Previously irradiated lesions must have shown progression to be considered measurable.\n* Documented activating EGFR and\u002For HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States \\[US\\] sites) or an equally accredited (outside of the US) local laboratory.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n* Minimum life expectancy of 12 weeks.\n* Adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 days before the first dose of study treatment:\n\n  1. Hemoglobin ≥ 9.0 g\u002FdL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.\n  2. Platelets ≥ 100 × 10\\^9 cells\u002FL.\n  3. Absolute neutrophil count ≥ 1.5 ×10\\^9 cells\u002FL. Criteria must be met without the use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to testing.\n* Adequate kidney function as assessed by following laboratory test to be conducted within 7 days before the first dose of study treatment:\n\n  a. Estimated glomerular filtration rate (eGFR) \\> 50 mL\u002Fmin per 1.73 m\\^2 according to the Modification of Diet in renal Disease Study Group (MDRD) formula.\n* Adequate liver function as assessed by following laboratory tests to be conducted within 7 days before the first dose of study treatment:\n\n  1. Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN for participants with documented Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia considered due to liver metastasis).\n  2. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN (or ≤ 5 × ULN if due to liver involvement by tumor).\n\nExclusion Criteria:\n\n* Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal phase, elimination half-lives, whichever is shorter, prior to the first dose of study drug.\n* Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described above) ≤ 14 days prior to the first dose of study drug.\n* Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation ≤ 14 days prior to the first dose of study drug.\n* Treatment with immunotherapy ≤ 28 days prior to the first dose of study drug.\n* Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.\n* Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic), presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local treatment (such as radiotherapy or surgery).\n* History of spinal cord compression or brain metastases with the following exceptions:\n\n  1. Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent) for at least 7 days prior to first dose of sevabertinib are eligible to enroll in Dose Escalation and Backfill.\n  2. Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion\u002FExtension (with the exception of Group G and Group H) if all of the following criteria are met:\n\n     * there is no evidence of progression (new or enlarging brain metastases) for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.\n     * Participants must be off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to first dose of sevabertinib.\n  3. Participants with history of spinal cord compression \\>3 months from definitive therapy and stable by imaging (MRI or CT) during the screening period and clinically asymptomatic.\n  4. Expansion Group G and Group H: Participants with active (new or progressing) clinically stable brain metastases who do not require immediate CNS-directed treatment as per Investigator's judgement and who are off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent such as ≤ 1.5 mg\u002Fday dexamethasone) in the 7 days prior to first dose of sevabertinib are eligible.\n* History of congestive heart failure (CHF) Class \\>II according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment (e.g. ventricular arrhythmias, atrial fibrillation) or any clinically important abnormalities in rhythm, conduction or morphology or resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \\>250 msec).\n* Participants with:\n\n  1. Known human immunodeficiency virus (HIV), except as noted below: Participants with history of HIV infection are eligible at the Investigator's discretion provided that: • CD4+ T-cell (CD4+) counts are ≥ 350 cells\u002FuL • The participant has been on established antiretroviral therapy (ART) for at least 4 weeks prior to the start of study drug and has an HIV viral load less than 400 copies\u002FmL prior to start of the study treatment • The ART being used does not contain strong inducers or inhibitors of CYP3A4, and is not anticipated to cause overlapping toxicities with study drug • The participant has not had an opportunistic infection within the past 12 months\n  2. Active Hepatitis B infection (positive for Hepatitis B surface antigen \\[HbsAg\\]) and Hepatitis B virus \\[HBV\\] DNA).\n  3. Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).\n\n     NOTE: Participants with history of chronic HBV or HCV infection are eligible at the Investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.\n* Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of study drug.","ALL","18 Years",{"count":19,"type":20},400,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body.\n\nEpidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are proteins that help cells to grow and divide. A damage (also called mutation) to the building plans (genes) for these proteins in cancer cells leads to a production of abnormal EGFR and\u002For HER2. These abnormal proteins drive the growth and the spread of the cancer. Several EGFR and\u002For HER2 mutations exist in the cancer cells. The study treatment, sevabertinib (BAY2927088), is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC.\n\nThe main purpose of this study is to learn:\n\nEscalation, Backfill, and Expansion Part:\n\n* How safe is BAY2927088 for the participants?\n* What is the highest dose of BAY2927088 that can be tolerated (maximum tolerated dose) by or given to (maximum administered dose) the participants?\n* How does BAY2927088 move into, through, and out of the bodies of the participants?\n\nFor this, the researchers will measure the followings:\n\n* The number of participants with medical problems, also called adverse events and serious adverse events, and their severity\n* The number of participants who discontinue study treatment due to an adverse event.\n* The highest dose of BAY2927088 that the participants can take without having adverse events (maximum tolerated dose (MTD)) or the maximum dose that is tested and found to be safe for the participants in case MTD cannot be found out (maximum administered dose (MAD)) of BAY2927088\n* Number of participants experiencing adverse events that prevent an increase in the dose of BAY2927088 (dose-limiting toxicities (DLTs)) at each dose level\n* The (average) total level of BAY2927088 in the blood (also called AUC) after receiving single or multiple doses of BAY2927088\n* The (average) highest level of BAY2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088 Extension Part\n* How well does BAY2927088 work in participants?\n\nFor this, the researchers will measure the following:\n\n• Percentage of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)). This will be assessed by doctors other than the study doctor.\n\nThis study has 4 parts:\n\n* The escalation part aims to find the maximum daily amount (dose) of BAY2927088 that participants can receive.\n* The backfill part aims to test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants. This will help find optimal doses of BAY2927088 that work well and are safe to be tested in the next part.\n* The expansion part aims to determine the dose of BAY2927088 to be tested in further studies.\n* The extension part aims to determine whether the selected dose of BAY2927088 from the expansion part works well.\n\nThe participants in this study will take the study treatment BAY2927088 in 3-week periods called \"cycles\". They will in general take BAY2927088 once or twice daily as a liquid\u002Ftablet by mouth until their cancer gets worse, they have medical problems, they leave the study, or the study is terminated. Participants will have no more than 5 visits per cycle.\n\nDuring the study, the study team will:\n\n* take blood and urine samples,\n* check the status of the cancer by doing computed tomography (CT) or magnetic resonance imaging (MRI) scans,\n* check the participants' overall health and heart health,\n* ask the participants questions about how they are feeling and what adverse events they are having.\n\nAn adverse event is considered \"serious\" when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important.",[27,28,29],"Advanced Non-small Cell Lung Cancer","EGFR Mutation","HER2 Mutation","RECRUITING","2026-06-30",{"date":33,"type":34},"2026-07-01","ACTUAL",{"date":36,"type":34},"2021-10-25",{"date":38,"type":20},"2029-06-29",{"name":40,"class":41},"Bayer","INDUSTRY",94,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":50,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":54,"conditions":55,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":60,"lastUpdatePostDateStruct":61,"startDateStruct":63,"completionDateStruct":65,"leadSponsor":67,"locationsCount":70},"100621037","phase-2-furmonertinib-160mg-vs-80mg--chemotherapy-in-egfr-mutated-nsclc-with-brain-metastases-efficacy-and-safety-study-100621037","NCT07365410","Furmonertinib 160mg vs 80mg + Chemotherapy in EGFR-Mutated NSCLC With Brain Metastases: Efficacy and Safety Study","Furmonertinib 160mg Versus Furmonertinib 80mg Combined With Chemotherapy (Carboplatin + Pemetrexed) as First-Line Treatment for EGFR-Mutated NSCLC Patients With Brain Metastases: A Multicenter Study of Efficacy and Safety","IInclusion Criteria\n\n* Aged 18 to 75 years (male or female)\n* Histopathologically confirmed, unresectable, and non-radiocurable newly -diagnosed locally advanced or metastatic lung adenocarcinoma\n* Confirmed by local laboratory to have one of the following EGFR mutations: -19Del or L858R (single or mixed mutations are allowed)\n* Treatment-naive for locally advanced (not suitable for surgery\u002Fradiotherapy per investigator) or metastatic NSCLC; adjuvant\u002Fneoadjuvant therapy completed \\>6 months before first progression is allowed (≤6 months is considered pretreated)\n* At least one measurable tumor lesion per RECIST 1.1 (lesions previously treated with radiotherapy are excluded; if only one measurable lesion exists, biopsy is allowed but baseline imaging must be performed ≥14 days after biopsy)\n* Confirmed stable and asymptomatic brain metastases\n* Sufficient organ function (per laboratory tests): ANC ≥1.5×10⁹\u002FL, PLT ≥100×10⁹\u002FL, HGB ≥90g\u002FL; TBIL ≤1.5×ULN, AST\u002FALT ≤2.5×ULN (for liver metastasis: TBIL ≤3×ULN, AST\u002FALT ≤5×ULN); CrCL ≥50 ml\u002Fmin (Cockcroft-Gault formula)\n* ECOG performance status 0-2 (no significant disease deterioration in 2 weeks before screening)\n* Expected survival \\>12 weeks after first dose\n* Non-pregnant women of childbearing potential (no pregnancy plan); women and men agree to use effective contraception during the study and 6 months after drug discontinuation\n* Voluntarily signs informed consent and understands the study procedures Exclusion Criteria（排除标准）\n* NSCLC with predominantly squamous cell histology, small cell lung cancer, neuroendocrine carcinoma, or other non-adenocarcinoma histologies\n* Concurrent positive for other driver genes (ALK fusion, ROS1 fusion, RET rearrangement, BRAF mutation, NTRK fusion, MET mutation, KRAS mutation); TP53, RB1, and BRAC mutations are excluded\n* Expected to receive other anti-tumor therapies during the trial\n* Major surgery (except vascular access or biopsy) within 4 weeks before first dose or planned during the trial\n* Use of CYP3A4 strong inhibitor within 7 days or strong inducer within 21 days before first dose; use of anti-tumor Chinese medicine within 2 weeks before first dose or planned during the trial\n* Participation in other clinical trials (investigational drug\u002Fdevice) within 4 weeks or 5 half-lives before first dose\n* Use of other anti-tumor drugs within 14 days before first dose\n* Spinal cord compression or symptomatic leptomeningeal metastasis\n* Toxicity from previous anti-tumor therapy not recovered to ≤CTCAE Grade 1 (except alopecia or platinum-induced peripheral neuropathy)\n* Symptomatic or unstable pleural\u002Fperitoneal effusion (stable ≥14 days after drainage is allowed)\n* History of other malignancies (except cured malignancies with no recurrence in 5 years: cervical carcinoma in situ, basal cell carcinoma, papillary thyroid carcinoma)\n* History of interstitial lung disease (ILD), drug-induced ILD, steroid-requiring radiation pneumonitis, or suspected ILD\n* Uncontrolled severe systemic diseases (e.g., hypertension, diabetes, NYHA III-IV heart failure, unstable angina, myocardial infarction within 1 year, active bleeding)\n* QTc \\>470 msec on resting ECG\n* Clinically significant QT prolongation or arrhythmias increasing QT risk (e.g., complete left bundle branch block, III° AV block, congenital long QT syndrome, severe hypokalemia, use of drugs causing QT prolongation)\n* Severe gastrointestinal dysfunction that impairs drug intake or absorption Infections requiring intravenous medication\n* Active mental illness or drug addiction\n* Known or suspected allergy to furmonertinib or its components\n* Pregnant or lactating women; women or their partners planning pregnancy during the study\n* Poor compliance (unable to follow study procedures)\n* Other conditions deemed unsuitable for enrollment by the investigator","75 Years",{"count":52,"type":20},60,[24],"This multicenter study evaluates the efficacy and safety of furmonertinib 160mg versus furmonertinib 80mg plus chemotherapy (carboplatin + pemetrexed) as first-line treatment for EGFR-mutated NSCLC patients with brain metastases. It aims to determine which approach is more effective and safer.",[56,57,58,28],"Non-small Cell Lung Cancer (NSCLC)","Brain Metastases","Furmonertinib","NOT_YET_RECRUITING","2026-01-23",{"date":62,"type":34},"2026-01-26",{"date":64,"type":20},"2026-01",{"date":66,"type":20},"2028-12",{"name":68,"class":69},"Tianjin Medical University Cancer Institute and Hospital","OTHER",1,{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":4,"eligibilityCriteria":77,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":78,"targetDuration":4,"studyType":21,"phases":80,"briefSummary":81,"conditions":82,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":86,"lastUpdatePostDateStruct":87,"startDateStruct":89,"completionDateStruct":91,"leadSponsor":93,"locationsCount":70},"100614865","phase-1-a-study-to-evaluate-ans014004-in-combination-with-egfr-tki-in-non-small-cell-lung-cancer-100614865","NCT07285148","A Study to Evaluate ANS014004 in Combination With EGFR-TKI in Non-Small Cell Lung Cancer","An Open-label, Multicenter Phase Ib\u002FII Study to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of ANS014004 in Combination With EGFR-TKI in Patients With EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer","Inclusion Criteria\n\nParticipants are eligible to be included in the study only if all of the following criteria apply:\n\n1. Male or female participants ≥18years of age at the time of signing the informed consent form.\n2. Patients with histologically or cytologically confirmed diagnosis of unresectable locally advanced (Stage IIIB and IIIC) or metastatic (Stage IV) NSCLC (according to the lung cancer staging criteria, refer to the eighth edition of the American Joint Committee on Cancer \\[AJCC\\] Lung Cancer Staging).\n3. Have a documented EGFR positive mutation (EGFR classic mutations including ex19del and ex21 L858R, uncommon mutations and ex20 insertion mutations) in tumor tissue samples or pleural fluid or blood samples.\n4. For Phase Ib dose escalation: have disease progression after the existing standard of care or intolerance to the existing standard of care or inappropriate or no effective standard of care is available (standard of care is defined as treatment recommended by the National Comprehensive Cancer Network \\[NCCN\\] guidelines \\[including but not limited to chemotherapy, radiotherapy, targeted therapy based on mutation status, immunotherapy, and surgery\\]). For participants who are considered intolerant to or ineligible for available standard therapy, or for whom effective standard therapy does not exist, the documentation of these reasons is required.\n\n   For Phase Ib dose optimization and Phase II study: have or haven't received prior standard systemic therapy for advanced disease.\n\n   Standard systemic therapy is referred to as (country-specific approved treatment will also be applied):\n   * EGFR classic mutations: EGFR-TKIs alone or in combination (examples, gefitinib and osimertinib with or without chemotherapy) for ex19del and ex21 L858R. Osimertinib or other third-generation EGFR TKI for T790M mutation.\n   * EGFR uncommon mutations: EGFR-TKIs or chemotherapy for uncommon mutations including but not limited to G719X, S768I, L861Q mutations.\n   * EGFR exon 20 activating insertions: chemotherapy with or without amivantamab or country-specific approved EGFR TKIs.\n5. For China only: the presence of MET amplification and\u002For overexpression in tumor tissue samples or pleural fluid or blood samples collected after progression on prior EGFR-TKI treatment, confirmed by a central \u002Flocal laboratory.\n\n   MET amplification is defined as the presence of MET amplification confirmed by nextgeneration sequencing (NGS) technology or mean MET gene copy number (GCN) ≥ 4 per cell or the ratio of MET to chromosome enumerating probe against chromosome 7 (MET\u002FCEP7) ≥2.0 confirmed by fluorescence in situ hybridization (FISH) testing.\n\n   MET overexpression is defined as immunohistochemistry (IHC) ≥ 2+ (local or central lab test results are accepted).\n6. Have at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\n7. ECOG PS ≤ 1.\n8. Life expectancy of ≥12 weeks, in the opinion of the investigator.\n9. Adequate organ function as determined by medical evaluation (within 7 days prior to study treatment) including:\n\n   * Adequate hematologic status, defined as: absolute neutrophil count (ANC) ≥1.5×109\u002FL, hemoglobin ≥90 g\u002FL, platelets ≥75×109\u002FL. Platelet transfusions are not permitted within 3 days, red blood cell transfusions are not permitted within 14 days, hematopoietic growth factors are not permitted within 7 days (14 days for PEGylated granulocyte colony stimulating factor \\[G-CSF\\] or erythropoietin) prior to obtaining these laboratory values.\n   * Adequate hepatic function, defined as: serum TBIL ≤1.5× ULN (in participants with known Gilbert's syndrome, TBIL ≤3× ULN with direct bilirubin ≤1.5× ULN), serum ALT or AST ≤2.5× ULN (or 5.0× ULN for documented liver metastasis).\n   * Adequate renal function, defined as: creatinine clearance ≥60 mL\u002Fmin (calculated by Cockcroft-Gault formula or CKD EPI formula \\[Appendix 4 of Section 12.4\\]).\n   * Adequate coagulation profile, defined as (including if receiving anticoagulant therapy):\n\n   prothrombin time (PT)\\\u003C 1.5 × ULN, activated partial thromboplastin time (APTT)\\\u003C 1.5 × ULN. If the participant is on anticoagulant therapy, must be on a stable dose of anticoagulant for at least1month prior to the study treatment.\n10. Female participants should be using adequate contraceptive measures until 90 days after the EOT, should not be breast feeding and must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to start of dosing if of childbearing potential; or must have evidence of non-child bearing potential by fulfilling one of the following criteria at screening.\n\n    * Achieved postmenopausal status, refer to NCCN Guidelines for Breast Cancer (2024V3.0) for the detailed definition of menopause.\n    * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.\n11. Male participants of childbearing potential are required to use adequate contraception (i.e., barrier method of birth control), during their participation in the study and for 90 days following the EOT. Male participants must also refrain from donating sperm during their participation in the study and for 90 days following the last dose of study treatment.\n12. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this study.\n\nExclusion Criteria\n\nParticipants are excluded from the study if any of the following criteria apply:\n\n1. Have other known primary driver gene alterations. For example, NSCLC with a targetable alteration in ALK, RET, ROS1, BRAF, KRAS, etc. The investigators should discuss enrollment with the sponsor regarding co-mutations.\n2. Prior treated with hepatocyte growth factor (HGF) targeted therapy or other MET-TKIs (including Type I and Type II), e.g., gulmonertinib, savolitinib, capmatinib, tepotinib, bozitinib, cabozantinib, glenitinib and almonertinib.\n3. Participation in other therapeutic clinical trials within 28 days prior to the first dose of study treatment.\n4. Received anti-tumor therapy (chemotherapy, immunotherapy, hormone therapy, targeted therapy, biological therapy or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, and agonists required to inhibit serum testosterone levels) within 14 days or 5 half-lives (whichever is shorter) of the first dose of study treatment. The following exceptions are:\n\n   * Nitrosourea or mitomycin-C within 6 weeks prior to the first dose of study treatment.\n   * Chinese medicines with anti-tumor indications within 7 days prior to the first dose of study treatment.\n5. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first dose of study treatment.\n\n   Participants must have recovered from all radiation related toxicity, not requiring corticosteroids.\n6. Major surgery, other than diagnostic surgery, within 4 weeks of the first study treatment or is expected during the study.\n7. Toxicities of prior therapy have not been resolved to Grade ≤1 or to baseline, as evaluated by NCI-CTCAE v5.0. NOTE: Participants with Grade 2 toxicities can be enrolled if the toxicities as stable and do not affect the safety of participating in this study (e.g., alopecia, skin hyperpigmentation, neuropathy).\n8. History of another primary malignancy that has been diagnosed or required therapy within the past 3 years (other than adequately treated local basal cell or squamous cell carcinoma of the skin; or any other cancer in situ currently in complete remission).\n9. Have central nervous system (CNS) metastases that are symptomatic or clinically unstable or require increased steroid dose to manage CNS symptoms within 4 weeks prior to the first dose of study treatment.\n\n   * Participants with symptomatic CNS metastases may participate in the study providing that symptoms are controlled after treatment, clinically stable for at least 4 weeks and have no evidence of new or enlarged brain metastases.\n   * Participants with carcinomatous meningitis or meningeal metastases, or spinal cord compression are excluded regardless of clinical stability.\n   * Participants with asymptomatic CNS metastases with a maximum diameter of brain metastases \\\u003C3 cm by imaging (such as MRI) without significant cerebral edema are eligible for the study.\n10. Participants with clinically uncontrollable third-space effusion, including but not limited to pleural effusion, peritoneal effusion or pericardial effusion, are assessed by the investigator to be unsuitable for the study treatment.\n11. Participants receiving unstable or increasing doses of corticosteroids. For participants receiving corticosteroids for endocrine deficiencies or symptoms associated to their disease (excluding CNS disease), the dose must have been stabilized (or reduced) for at least 14 days before the first dose of study treatment.\n12. Have a history of or ongoing severe retinopathy.\n13. Presence of serious cardiovascular or cerebrovascular disease, including but not limited to:\n\n    * Mean resting corrected QT interval corrected by Fridericia's formula (QTcF) \\>470 msec obtained from triplicate 12-lead electrocardiograms (ECGs).\n    * Symptomatic heart failure per New York Heart Association (NYHA) classification Class II or above.\n    * Baseline left ventricular ejection fraction (LVEF) below institution's lower limit of normal (LLN) or \\\u003C50% if assessed by echocardiography (ECHO) or Multigated Radionuclide Angiography (MUGA).\n    * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.\n    * Presence of any factors that increase the risk of QTc prolongation or the risk of arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or use of any concomitant medication known to prolong the QT interval within 14 days prior to the first dose of study treatment.\n    * Any of the following within 6 months prior to the first dose of the study treatment: myocardial infarction, severe\u002Funstable angina, coronary artery bypass graft, congestive heart failure, cardiomyopathy, pulmonary embolism, cerebrovascular accident, or transient ischemic attack.\n14. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including but not limited to:\n\n    * Uncontrolled hypertension, defined as a systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite medical therapy. Participant with a history of hypertension is allowed if BP is stable and controlled within these limits by antihypertensive treatment.\n    * Previous history of, or presence of clinically symptomatic or at high risk for interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic treatment).\n    * Unstable or uncompensated respiratory and renal disease, active bleeding diseases.\n15. Uncontrolled concurrent infection including but not limited to:\n\n    * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.\n\n      * If hepatitis B surface antigen (HBsAg) is positive, HBV DNA assay should be performed. Participants may be eligible if HBV DNA test value ≤ ULN.\n      * If HCV antibody is positive, HCV ribonucleic acid (RNA) assay should be performed. Participants may be eligible if HCV RNA negative.\n    * Known human immunodeficiency virus (HIV) infection or known history of acquired immunodeficiency syndrome (AIDS).\n    * Syphilis positive.\n    * Active tuberculosis infection.\n    * Onset period of keratitis or ulcerative keratitis.\n    * Other active infections requiring systemic treatment within 14 days prior to the first dose of study treatment.\n16. Unwilling or unable to comply with the requirements of oral drug administration, or presence of gastrointestinal disorders such as refractory nausea and vomiting, any acute or chronic gastrointestinal disorder, inability to swallow the formulation, or prior major bowel resection that may prevent adequate absorption of ANS014004 or PLB1004.\n17. Hypersensitivity to ANS014004, PLB1004 or their excipients, or history of allergic reactions to ANS014004 and PLB1004 with similar chemical or biological structure or similar drugs.\n18. Concomitant use of drugs metabolized by P-glycoprotein (P-gp)\u002Fbreast cancer resistance protein (BCRP) or OCT2\u002FOATP1B1\u002FMATE1, or moderate or strong inducers or inhibitors of P-gp\u002FBCRP or CYP2B6\u002FCYP2C9\u002FCYP2C19\u002FOCT2\u002FOATP1B1\u002FMATE1 within 5 half-lives before the use of the study treatment. For dose escalation part only: concomitant treatment with moderate or strong P-gp\u002FBCRP or CYP2C8\u002FCYP2D6\u002FCYP3A4 inducers or inhibitors within 5 half-lives prior to administration of study treatment.\n19. In receipt of any live attenuated vaccination within 30 days prior to the first dose of study therapy.\n20. Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.\n21. Have prior or ongoing clinically significant illness, medical condition, surgical history, physical findings, or laboratory abnormality that, in the investigator's opinion, would not be in the best interest of the participant; or that could alter the absorption, distribution, metabolism, or excretion of the study treatment; or impair the assessment of study results.",{"count":79,"type":20},253,[23,24],"Protocol Title\n\nA Study to Evaluate ANS014004 in Combination with EGFR-TKI in Patients with EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer\n\nThe main purpose of this research study is to\n\nFind a safe and tolerable dose of two investigational drugs, ANS014004 and PLB1004, when used together.\n\nLearn how effective this drug combination is at treating a type of lung cancer called \"EGFR mutation-positive non-small cell lung cancer (NSCLC)\" that has spread to other parts of the body (locally advanced or metastatic).\n\nThis study is trying to answer the following questions:\n\nSafety \\& Dosing: What are the side effects of combining ANS014004 and PLB1004? What is the best dose to use that patients can tolerate well?\n\nEffectiveness: Can this combination of drugs help shrink patients' tumors or stop them from growing?\n\nBackground Information\n\nFor patients with advanced lung cancer that has a specific gene change called an \"EGFR mutation,\" targeted therapies known as EGFR-TKIs are a standard treatment. While these treatments often work well at first, most tumors eventually stop responding to the drug (this is called \"acquired resistance\"). The investigational drug ANS014004 is designed to block a protein called MET, which is one of the ways that tumors become resistant to EGFR-TKIs. The researchers believe that by combining ANS014004 with the EGFR-TKI PLB1004, they may be able to prevent or delay resistance, offering patients a more effective and longer-lasting treatment option.\n\nHow will the study be conducted?\n\nThis study is divided into two parts:\n\nPart 1 (Dose Escalation and Optimization): A small number of participants will receive different dose levels of ANS014004 combined with a fixed dose of PLB1004. The goal is to find the safest and most tolerable dose combination.\n\nPart 2 (Phase II Study): Once a recommended dose is identified, more participants will be enrolled to further evaluate how well the drug combination works against the cancer.\n\nThroughout the study, participants' health will be closely monitored, and their tumors will be measured regularly using imaging scans (like CT scans) to see how they respond to the treatment.",[83,28,84,85],"Non-Small Cell Lung Cancer","Metastatic Lung Cancer","MET Alteration","2025-12-09",{"date":88,"type":34},"2025-12-16",{"date":90,"type":20},"2026-06",{"date":92,"type":20},"2029-12",{"name":94,"class":41},"Beijing Pearl Biotechnology Limited Liability Company",{"id":96,"slug":97,"hasResults":11,"nctId":98,"briefTitle":99,"officialTitle":100,"acronym":101,"eligibilityCriteria":102,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":103,"targetDuration":4,"studyType":21,"phases":105,"briefSummary":106,"conditions":107,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"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":104,"type":20},100,[24],"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.",[108,28,109,110],"Non Small Cell Lung Cancer","Leptomeningeal Metastases","Targeted Therapy","2025-05-06",{"date":113,"type":34},"2025-05-14",{"date":115,"type":20},"2025-05-15",{"date":117,"type":20},"2027-06-01",{"name":119,"class":120},"Qiming Wang","OTHER_GOV"]