{"doi":"10.1093/neuonc/noaf025","title":"Intrathecal sintilimab for leptomeningeal metastases of non-small cell lung cancer failed from targeted therapy and intrathecal chemotherapy (LMIS study)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Leptomeningeal metastases (LMs) are serious complications of non-small cell lung cancer (NSCLC). This study aimed to investigate the safety and efficacy of intrathecal immune checkpoint inhibitors (ICIs) in treating NSCLC-LM.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>We conducted this prospective phase 1 study (ChiCTR2200062245) using a traditional “3+3” design with intrathecal sintilimab (dose escalation 10, 20, 30, and 40 mg) for NSCLC-LM patients who had progressed from targeted therapy and intrathecal pemetrexed. The primary study endpoints were safety and recommended dose, and the secondary endpoints included clinical response rate, progression-free survival (PFS), intracranial progression-free survival (iPFS), and overall survival (OS).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>No dose-limiting toxicity was found at 10, 20, 30, and 40 mg for intrathecal sintilimab. Therefore, sintilimab 40 mg was recommended for intrathecal injection. A total of 19 patients were enrolled in this study. The median age at diagnosis of LM was 53 years. The overall incidence of adverse events (AEs) was 68.4%, and rash (n = 4, 21.1%) was the most common AEs, which returned to normal after symptomatic treatment. As 1 patient was lost to follow-up and 18 patients could be evaluated for efficacy, the clinical response rate was 38.9% (7/18). Median PFS was 3.5 months (95% CI: 2.7–4.2 months), median iPFS was 3.5 months (95% CI: 1.3–5.6 months), and median OS was 11.5 months (95% CI: 0.0–25.4 months).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Intrathecal ICIs for NSCLC-LM patients are safe, and the recommended dose of sintilimab is 40 mg. Intrathecal sintilimab for NSCLC-LM failed from multi-line therapies, showed potential effectiveness in some patients, and is worthy of further study.</jats:p>\n               </jats:sec>","journal":"Neuro-Oncology","year":2025,"id":603880,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":441352,"name":"Yuanyuan Hu","orcid":"0000-0001-6788-702X","position":1,"is_corresponding":false},{"id":409693,"name":"Chong Teng","orcid":"0000-0001-9898-6442","position":2,"is_corresponding":false},{"id":1549230,"name":"Yanju Lv","orcid":null,"position":3,"is_corresponding":false},{"id":86635,"name":"Xiaowei Song","orcid":"0000-0001-9589-2520","position":4,"is_corresponding":false},{"id":1549233,"name":"Weixi Shen","orcid":null,"position":5,"is_corresponding":false},{"id":1549234,"name":"Qiuying Jiang","orcid":null,"position":6,"is_corresponding":false},{"id":542510,"name":"Dayong Huang","orcid":"0000-0001-9449-8484","position":7,"is_corresponding":false},{"id":1549235,"name":"Lina Du","orcid":null,"position":8,"is_corresponding":false},{"id":758482,"name":"Guohua Wang","orcid":"0000-0001-6721-8002","position":9,"is_corresponding":false},{"id":245945,"name":"Yang Du","orcid":"0000-0001-9219-4989","position":10,"is_corresponding":false},{"id":1549238,"name":"Siqi Man","orcid":null,"position":11,"is_corresponding":false},{"id":383925,"name":"Zhichao Zhang","orcid":"0000-0003-2699-6822","position":12,"is_corresponding":false},{"id":500806,"name":"Jing Zhang","orcid":"0000-0002-4823-4629","position":13,"is_corresponding":false},{"id":697735,"name":"Li Li","orcid":"0000-0001-6598-6358","position":14,"is_corresponding":false},{"id":1549242,"name":"Tao Xin","orcid":"0000-0003-2798-5068","position":15,"is_corresponding":false},{"id":1549227,"name":"Chengjuan Fan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Intrathecal sintilimab for leptomeningeal metastases of non-small cell lung cancer failed from targeted therapy and intrathecal chemotherapy (LMIS study)","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Leptomeningeal metastases (LMs) are serious complications of non-small cell lung cancer (NSCLC). This study aimed to investigate the safety and efficacy of intrathecal immune checkpoint inhibitors (ICIs) in treating NSCLC-LM.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>We conducted this prospective phase 1 study (ChiCTR2200062245) using a traditional “3+3” design with intrathecal sintilimab (dose escalation 10, 20, 30, and 40 mg) for NSCLC-LM patients who had progressed from targeted therapy and intrathecal pemetrexed. The primary study endpoints were safety and recommended dose, and the secondary endpoints included clinical response rate, progression-free survival (PFS), intracranial progression-free survival (iPFS), and overall survival (OS).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>No dose-limiting toxicity was found at 10, 20, 30, and 40 mg for intrathecal sintilimab. Therefore, sintilimab 40 mg was recommended for intrathecal injection. A total of 19 patients were enrolled in this study. The median age at diagnosis of LM was 53 years. The overall incidence of adverse events (AEs) was 68.4%, and rash (n = 4, 21.1%) was the most common AEs, which returned to normal after symptomatic treatment. As 1 patient was lost to follow-up and 18 patients could be evaluated for efficacy, the clinical response rate was 38.9% (7/18). Median PFS was 3.5 months (95% CI: 2.7–4.2 months), median iPFS was 3.5 months (95% CI: 1.3–5.6 months), and median OS was 11.5 months (95% CI: 0.0–25.4 months).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Intrathecal ICIs for NSCLC-LM patients are safe, and the recommended dose of sintilimab is 40 mg. Intrathecal sintilimab for NSCLC-LM failed from multi-line therapies, showed potential effectiveness in some patients, and is worthy of further study.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39899029","pmcid":"PMC12309713","openalex_id":"https://openalex.org/W4407087251","authors":[],"funders":[{"funder_name":"Wu Jieping Medical Foundation","grant_id":"320.6750.2022-16-3","title":null},{"funder_name":"Beijing Association for Cancer Control and Prevention","grant_id":"CAPTRALung2021008","title":null}],"total_grants":2,"fwci":7.3441,"citation_percentile":0.97136775,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":5}],"oa_status":"green","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12309713/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12309713/","host_type":"repository"},{"url":"https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noaf025/61741674/noaf025.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/neuro-oncology/article-pdf/27/6/1559/61741674/noaf025.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/neuonc/noaf025","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39899029","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12309713","host_type":"repository"}],"fields_of_study":["Brain Metastases and Treatment","Lung Cancer Diagnosis and Treatment","Lung Cancer Research Studies"],"mesh_terms":["Adult","Aged","Carcinoma, Non-Small-Cell Lung","Female","Follow-Up Studies","Humans","Injections, Spinal","Lung Neoplasms","Male","Meningeal Neoplasms","Middle Aged","Prognosis","Prospective Studies","Survival Rate","Molecular Targeted Therapy","Antibodies, Monoclonal, Humanized"],"keywords":["Medicine","Rash","Intrathecal","Lung cancer","Adverse effect","Clinical endpoint","Chemotherapy","Incidence (geometry)","Internal medicine","Surgery","Oncology","Clinical trial","Non-small cell lung cancer","Immune Checkpoint Inhibitors","Intrathecal Treatment","Sintilimab","Leptomeningeal Metastatses"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T22:55:06.439619Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}