[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100574653":3},{"organization":4,"armGroups":7,"interventions":15,"overallOfficials":26,"centralContacts":31,"locations":40,"responsibleParty":57,"collaborators":21,"id":60,"slug":61,"hasResults":62,"nctId":63,"briefTitle":64,"officialTitle":65,"acronym":21,"eligibilityCriteria":66,"healthyVolunteers":62,"sex":67,"minAge":68,"maxAge":69,"enrollmentInfo":70,"targetDuration":21,"studyType":73,"phases":74,"briefSummary":77,"conditions":78,"keywords":80,"overallStatus":42,"whyStopped":21,"lastUpdateSubmitDate":85,"lastUpdatePostDateStruct":86,"startDateStruct":89,"completionDateStruct":91,"leadSponsor":93,"locationsCount":94},{"fullName":5,"class":6},"Guangzhou Medical University","OTHER",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"PD-1\u002FCTLA-4 Bispecific Antibody with Pemetrexed","EXPERIMENTAL","This study is a prospective, single-arm, Phase I\u002FII clinical trial. The primary objective is to determine the recommended Phase II dose (RP2D) for the intrathecal combination of PD-1\u002FCTLA-4 bispecific antibody with pemetrexed and and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), progression-free survival related to leptomeningeal metastasis (LMPFS) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and\u002For immune) of the efficacy and safety of this regimen.",[13,14],"Drug: Cadonilimab (AK104)","Drug: Pemetrexed (Alimta)",[16,22],{"type":17,"name":18,"description":19,"armGroupLabels":20,"otherNames":21},"DRUG","Cadonilimab (AK104)","Intrathecal injection of PD-1\u002FCTLA-4 bispecific antibody was administered every two weeks for six weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.",[9],null,{"type":17,"name":23,"description":24,"armGroupLabels":25,"otherNames":21},"Pemetrexed (Alimta)","Pemetrexed was administrated by intrathecal injection, first as induction therapy, twice per week for 2 weeks, followed by consolidation therapy, once per week for 4 weeks, then maintenance therapy, once per month until the patient's death, leptomeningeal metastasis progresses, or intolerable severe adverse events occurred.",[9],[27],{"name":28,"affiliation":29,"role":30},"Zhenyu Pan, PhD, MD","The Affiliated Huizhou Hospital, Guangzhou Medical University","PRINCIPAL_INVESTIGATOR",[32,36],{"name":28,"role":33,"phone":34,"phoneExt":21,"email":35},"CONTACT","+8618718178286","dr-zypan@163.com",{"name":37,"role":33,"phone":38,"phoneExt":21,"email":39},"Guozi Yang, PhD, MD","+8615804302755","2023621057@gzhmu.edu.cn",[41],{"facility":29,"status":42,"city":43,"state":44,"zip":45,"country":46,"countryCode":47,"cosmosGeoPoint":48,"geoPoint":53,"contacts":54},"RECRUITING","Huizhou","Guangdong","516000","China","CN",{"type":49,"coordinates":50},"Point",[51,52],114.41523,23.11147,{"lat":52,"lon":51},[55,56],{"name":28,"role":33,"phone":34,"phoneExt":21,"email":35},{"name":37,"role":33,"phone":38,"phoneExt":21,"email":39},{"type":30,"investigatorFullName":58,"investigatorTitle":59,"investigatorAffiliation":5,"oldNameTitle":21,"oldOrganization":21},"Zhenyu Pan","Professor","100574653","phase-1-intrathecal-combination-of-programmed-death-1-pd-1cytotoxic-t-lymphocyte-associated-protein-4-ctla-4-bispecific-antibody-and-pemetrexed-for-leptomeningeal-metastasis-100574653",false,"NCT06762080","Intrathecal Combination of Programmed Death-1 (PD-1)\u002FCytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis","Intrathecal Administration of PD-1\u002FCTLA-4 Bispecific Antibody Plus Pemetrexed in Patients With Leptomeningeal Metastasis From Solid Tumors: A Phase I\u002FII Study","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.\n2. Male or female aged between 18 and 75 years; Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n3. No history of severe nervous system disease; No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing \\>Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.\n4. The first month to treatment, as well as during induction and consolidation therapy, new drugs effective against leptomeningeal metastases were used, excluding those previously administered. These primarily included small molecule targeted therapies, such as EGFR-TKI\u002FALK-TKI drugs like Osimertinib and Lorlatinib.\n5. Patients with poor compliance or other reasons that were unsuitable for this study.","ALL","18 Years","75 Years",{"count":71,"type":72},36,"ESTIMATED","INTERVENTIONAL",[75,76],"PHASE1","PHASE2","Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors. This phase I\u002FII study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal Programmed Death-1 (PD-1)\u002FCytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) bispecific antibodies combined with pemetrexed in patients with leptomeningeal metastasis.",[79],"Leptomeningeal Metastasis",[81,82,83,84,79],"Cadonilimab","PD-1\u002FCTLA-4","Pemetrexed","Intrathecal","2025-05-15",{"date":87,"type":88},"2025-05-20","ACTUAL",{"date":90,"type":88},"2025-03-07",{"date":92,"type":72},"2026-06-01",{"name":5,"class":6},1]