[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"met-alteration\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:met-alteration":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,44,72],{"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":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100614865","phase-1-a-study-to-evaluate-ans014004-in-combination-with-egfr-tki-in-non-small-cell-lung-cancer-100614865",false,"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.","ALL","18 Years",{"count":19,"type":20},253,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","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.",[27,28,29,30],"Non-Small Cell Lung Cancer","EGFR Mutation","Metastatic Lung Cancer","MET Alteration","NOT_YET_RECRUITING","2025-12-09",{"date":34,"type":35},"2025-12-16","ACTUAL",{"date":37,"type":20},"2026-06",{"date":39,"type":20},"2029-12",{"name":41,"class":42},"Beijing Pearl Biotechnology Limited Liability Company","INDUSTRY",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":54,"conditions":55,"keywords":57,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":62,"lastUpdatePostDateStruct":63,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":71},"100567509","phase-1-fih-trial-of-vert-002-in-patients-with-locally-advanced-or-metastatic-solid-tumors-with-met-alterations-100567509","NCT06669117","FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations","A First-In-Human (FIH) Phase I\u002FII Open-label, Multicentre, Dose Escalation and Expansion Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors Including Non-small Cell Lung Cancer (NSCLC) Harboring Mesenchymal-Epithelial Transition (MET) Alterations","Inclusion Criteria:\n\n1. Part 1: histological confirmation of relapsed and\u002For refractory locally advanced or metastatic solid tumor for which no standard of care treatment is available.\n2. Part 2: histological confirmation of locally advanced or metastatic NSCLC Stage IIIB\u002FC or IV (American Joint Commission on Cancer \\[AJCC\\] 8th edition) in participants who are not eligible for or should have received available standard of care therapies including curative intent surgery, chemoradiation, radiotherapy or systemic therapy.\n3. Part 1: presence of at least one of the following MET alterations based on local documentation of blood or archived tissue results:\n\n   * METex14 mutation\n   * MET kinase domain activating gene mutations (e.g. H1094L\u002FR\u002FY, D1228H\u002FN\u002FV, Y1230A\u002FC\u002FD\u002FH)\n   * MET amplification\n4. Part 2-a: presence of METex14 mutation (based on local documentation of blood or archived tissue results) and for Part 2-b presence of at least one of the following MET alterations: METex14 mutation (based on local documentation of blood or archived tissue results), de novo MET amplification (based on local documentation of archived tissue results). Confirmation after enrollment in the trial will be performed by central testing from an archival tumor biopsy sample (either tissue block or at least 15 serial cut unstained slides of 5 μm, at least 20% tumor content). In case no archival biopsy is available for central testing, the patient must be willing to have a fresh tumor biopsy sample collected and the tumor biopsy should be deemed safe and feasible by the investigator.\n5. Part 2: at least one measurable target lesion according to RECIST v1.1.\n6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n7. Part 1: participants may have received MET Tyrosine Kinase Inhibitor (TKI) as part of previous treatment, regardless of the line of therapy (first or second line), and regardless of the MET TKI being combined or not. Note: crizotinib will be considered a MET TKI.\n8. Part 2: a maximum of 3 prior lines of systemic therapies.\n9. Adequate hematologic function.\n10. Adequate hepatic function.\n11. Adequate renal function.\n12. Albumin ≥ 3 g\u002FdL.\n13. Adequate coagulation function.\n14. Adequate cardiac function.\n15. Female participants of childbearing potential must have a negative highly sensitive serum β-HCG test performed within 7 days prior to the first dose of VERT-002 and a negative urine pregnancy test performed at C1D1 prior to the first dose of VERT-002.\n16. Male participants\u002Fpartners with female spouse\u002Fpartners of childbearing potential must agree to take appropriate precautions to avoid fathering a child.\n\nNOTE: Other protocol defined inclusion criteria may apply.\n\nExclusion Criteria:\n\n1. Part 2: Documented evidence by local testing of targetable oncogene driver mutations.\n2. History of a primary malignancy other than the cancer under trial (as defined for Parts 1 and 2) with the exception of:\n\n   * Participants with a previous malignancy who completed their anticancer treatment at least 2 years before signing informed consent and with no evidence of residual disease from the prior malignancy at screening.\n   * Malignancies with a negligible risk of metastasis or death (i.e. 5-year overall survival rate \\> 90%) that are adequately treated.\n3. Uncontrolled Central Nervous System (CNS) metastases or spinal cord compression that are associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease.\n4. History of hypersensitivity to active or inactive ingredients of VERT-002, or drugs with a similar chemical structure or from a similar class.\n5. Active, bacterial, fungal, or viral infection, within 2 weeks prior to the first dose of VERT-002 (C1D1).\n6. Positive SARs-CoV-2 or variants of SARs-CoV2 test within 2 weeks prior to first dose administration of VERT-002 (C1D1) or with suspected infection with SARs-CoV-2 or variants of SARs-CoV-2 and confirmation pending.\n7. Impaired cardiovascular function or clinically significant cardiovascular disease (either active or within 6 months prior to signing main informed consent).\n8. Uncontrolled intercurrent illness including, but not limited to psychiatric illness or social situation that would limit compliance with trial requirements.\n9. Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD.\n10. Women who are pregnant or breastfeeding.\n11. Prior anticancer therapy:\n\n    * MET TKI within 7 days prior to the first dose of VERT-002,\n    * Any other systemic anticancer therapy within 28 days or 5 half-lives of the anticancer therapy whichever is the shortest, but with a minimum of 14 days interval, prior to the first dose of VERT-002 (C1D1),\n    * Radiotherapy to a large field or including a vital organ (including whole brain radiotherapy or stereotactic radiosurgery to brain) within 14 days prior to the first dose of VERT-002 (C1D1).\n12. Live attenuated vaccine within 28 days prior to the first dose of VERT-002 (C1D1).\n13. Any toxicities from prior therapy with NCI- CTCAE Grade \\> 1 at the time of the first dose administration of VERT-002 (C1D1). Exceptions include any grade alopecia, fatigue and peripheral neuropathy with a grade ≤ 2.\n14. Major surgical procedure within 14 days of the first dose of VERT-002 (C1D1).\n15. Participation in a clinical trial with administration of an investigational drug within 5 half- lives plus 14 days of the investigational drug, prior to the first dose of VERT-002 (C1D1).\n\nNOTE: Other protocol defined exclusion criteria may apply.",{"count":52,"type":20},140,[23,24],"The goal of this clinical trial is to investigate the safety, the activity of VERT-002 (PFL-002), and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.",[56,30],"Solid Tumor",[58,59,60],"Locally advanced or metastatic solid tumors","MET alteration","Non-small cell lung cancer","RECRUITING","2025-06-29",{"date":64,"type":35},"2025-07-02",{"date":66,"type":35},"2024-10-22",{"date":68,"type":20},"2032-10-01",{"name":70,"class":42},"Pierre Fabre Medicament",19,{"id":73,"slug":74,"hasResults":11,"nctId":75,"briefTitle":76,"officialTitle":77,"acronym":78,"eligibilityCriteria":79,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":80,"targetDuration":4,"studyType":21,"phases":82,"briefSummary":83,"conditions":84,"keywords":102,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":110,"lastUpdatePostDateStruct":111,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":119},"100299221","phase-2-apl-101-study-of-subjects-with-nsclc-with-c-met-exon-14-skip-mutations-and-c-met-dysregulation-advanced-solid-tumors-100299221","NCT03175224","APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors","Phase 1 \u002F 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors","SPARTA","Major Inclusion Criteria:\n\n1. Men and women 18 years of age or older.\n2. 9 cohorts will be enrolled:\n\n   * Cohort A1 \u002F Exon 14 NSCLC MET inhibitor naive in first line: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b\u002F4); treatment-naive subjects in first line; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort A2 \u002F Exon 14 NSCLC - MET inhibitor naïve: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b\u002F4); pretreated subjects refractory to or intolerant of standard therapies with no more than three lines of prior therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort B \u002F Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED\n   * Cohort C \u002F MET amplification basket tumor types excluding primary CNS tumors: Any solid tumor type regardless of histology excluding primary CNS tumors, with MET amplification; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort C1 \u002F MET amplification and wild-type EGFR NSCLC: NSCLC regardless of histology, harboring MET amplification and wild-type EGFR; unresectable or metastatic disease, previously untreated or treated with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort C2 \u002F EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on Therapy): Unresectable or metastatic NSCLC regardless of histology, harboring EGFR activating mutations with acquired MET-Amplification as resistance mechanism to the EGFR-I; developed resistance to first-line EGFR-inhibitor therapy after an initial response (documented PR for at least 12 weeks); radiological documentation of disease progression per RECIST on first-line EGFR inhibitor therapy; currently on an EGFR-inhibitor therapy and agrees to receive APL-101 as an add-on therapy during the study; no history of interstitial lung disease (ILD)\u002Fpneumonitis, Grade ≥3 liver toxicity or QT prolongation with EGFR-I therapy; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort D \u002F MET fusion basket tumor types excluding primary CNS tumors: any solid tumor type regardless of histology excluding primary CNS tumors; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n   * Cohort E \u002F Primary CNS tumors with MET alterations: subjects with primary CNS tumors who meet inclusion criteria of MET dysregulations defined as single or co-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skipping mutations, or MET amplification; refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations; neurological symptoms controlled on a stable\u002Fdecreasing dose of steroids for at least 2 weeks before C1D1\n   * Cohort F \u002F Basket tumor types harboring wild-type MET with over-expression of HGF and MET: any solid tumor type regardless of histology harboring wild-type MET with overexpression of HGF and MET; Unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations\n3. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.\n4. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target lesion according to relevant criteria\n5. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.\n6. Acceptable organ function\n7. For all prior anticancer treatment, a duration of 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration.\n8. Adequate cardiac function\n9. Women of child-bearing potential must have a negative serum or Beta-hCG at screening or evidence of surgical sterility or evidence of post-menopausal status\n10. No planned major surgery within 4 weeks of first dose of APL-101\n11. Expected survival (life expectancy) ≥ 3 months from C1D1\n12. Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site) or liquid biopsy sample (if tumor tissue is insufficient or lacking, and approved by the sponsor) is required for prospective central lab confirmation for study entry (subjects with previously confirmed molecular status by the Sponsor designated central lab or FDA approved NGS based MET testing may be exempted, subjected to Sponsor approval.\n\nMajor Exclusion Criteria:\n\n1. Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.\n2. Known actionable mutation\u002Fgene rearrangement of EGFR (except for NSCLC subjects in Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.\n3. Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination.\n4. Active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process, which in the opinion of the investigator makes the risk: benefit unfavorable for the participation of the trial.\n5. Life-threatening illness, significant organ system dysfunction or comorbid conditions, or other reasons that, in the investigator's opinion, could compromise the subject's safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of APL-101.\n6. Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening, or concurrent treatment with a medication that is a known risk for prolonging the QT interval. Chronic controlled atrial fibrillation is not excluded.\n7. Historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with antiviral therapy and human immunodeficiency virus (HIV) positive subjects who are not clinically stable or controlled on their medication (asymptomatic subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells\u002FμL and have not had an opportunistic infection within the past 12 months prior to first dose of APL-101 would be eligible for study entry. If history is unclear, relevant test(s) at Screening will be required to confirm eligibility.\n8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.\n9. Unable to swallow orally administered medication whole.\n10. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption\n11. Women who are breastfeeding\n12. History of another malignancy within 3 years prior to C1D1. A subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years:\n\n    1. Carcinoma of the skin without melanomatous features.\n    2. Curatively treated cervical carcinoma in situ.\n    3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (T1s), thyroid papillary cancer with prior treatment, prostate cancer which has been surgically or medically treated and not likely to recur within 3 years.\n13. Subjects who are unable or unwilling to discontinue excluded medications (drugs with known QTc risk and known strong cytochrome P450 \\[CYP\\]3A4 inducer and\u002For strong inhibitors) for at least 5 half-lives prior to first dose of study drug. Subjects may qualify if such medication(s) can be safely replaced with alternate medications with less risk of drug-drug interaction.\n14. Subjects with active COVID-19 infection.\n15. Symptomatic and\u002For neurologically unstable CNS metastases, or who require an increase in steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose for at least 2 weeks prior to C1D1 may be allowed.",{"count":81,"type":20},497,[24],"To assess:\n\n* efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14 skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET\n* efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC harboring EGFR activating mutations and developed acquired resistance with MET amplification and disease progression after documented CR or PR with 1st line EGFR inhibitors (EGFR-I)",[85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,30,100,101],"Solid Tumors","Advanced Cancer","Renal Cancer","Gastric Cancer","Gastroesophageal Junction Adenocarcinoma","NSCLC","Lung Cancer","Brain Tumor","Glioblastoma Multiforme","EGFR Gene Mutation","MET Amplification","HGF","Thyroid Cancer","Pancreatic Cancer","Colon Cancer","MET Fusion","Exon 14 Skipping",[103,104,105,106,107,108,96,109],"Advanced Solid Tumor","Relapsed Solid Tumor","Recurrent Solid Tumor","cMet exon 14 skipping","cMet fusion","GBM","EGFR positive","2025-06-24",{"date":112,"type":35},"2025-06-27",{"date":114,"type":35},"2017-09-27",{"date":116,"type":20},"2026-11-30",{"name":118,"class":42},"Apollomics Inc.",35]