[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657645":3},{"organization":4,"outcomesModule":7,"designInfo":50,"detailedDescription":57,"studyPopulation":53,"armGroups":58,"interventions":66,"overallOfficials":53,"centralContacts":76,"locations":82,"responsibleParty":100,"collaborators":53,"id":104,"slug":105,"hasResults":106,"nctId":107,"briefTitle":108,"officialTitle":109,"acronym":110,"eligibilityCriteria":111,"healthyVolunteers":106,"sex":112,"minAge":113,"maxAge":53,"enrollmentInfo":114,"targetDuration":53,"studyType":117,"phases":118,"briefSummary":120,"conditions":121,"keywords":123,"overallStatus":130,"whyStopped":53,"lastUpdateSubmitDate":131,"lastUpdatePostDateStruct":132,"startDateStruct":135,"completionDateStruct":137,"leadSponsor":139,"locationsCount":140},{"fullName":5,"class":6},"Cancer Institute and Hospital, Chinese Academy of Medical Sciences","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":21,"otherOutcomes":41},[9,13,17],{"measure":10,"description":11,"timeFrame":12},"Incidence and Severity of Adverse Events","The number and percentage of participants who experience adverse events, serious adverse events, and treatment-related adverse events will be summarized overall and by dose level. Safety will also be evaluated using clinically significant changes in laboratory test results, vital signs, physical examinations, and other safety assessments.","From the first dose of ATRA through the safety follow-up visit, approximately 28 days after the last dose of study treatment",{"measure":14,"description":15,"timeFrame":16},"Incidence of Dose-Limiting Toxicities","The number and percentage of DLT-evaluable participants who experience a dose-limiting toxicity (DLT) will be summarized by ATRA dose level. DLTs will be assessed according to the protocol-defined criteria during the 28-day DLT evaluation period.","From the start of the 7-day ATRA lead-in period through the end of the first 21-day combination-treatment cycle, a total of 28 days",{"measure":18,"description":19,"timeFrame":20},"Maximum Tolerated Dose and\u002For Recommended Dose for Further Study","The maximum tolerated dose (MTD) and\u002For recommended dose for further study will be determined using the prespecified 3+3 dose-escalation rules. The determination will be based primarily on the occurrence of DLTs at each ATRA dose level, together with the overall available safety and tolerability data for ATRA in combination with tislelizumab.","At completion of dose escalation, based primarily on DLTs observed during each participant's 28-day DLT evaluation period",[22,26,29,33,37],{"measure":23,"description":24,"timeFrame":25},"Objective Response Rate","Objective response rate (ORR) is defined as the percentage of participants whose best overall response is a confirmed complete response (CR) or partial response (PR), as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).","From the first dose of study treatment until disease progression, initiation of a new anticancer treatment, death, withdrawal of consent, loss to follow-up, or study completion, whichever occurs first, assessed for up to approximately 24 months",{"measure":27,"description":28,"timeFrame":25},"Disease Control Rate","Disease control rate (DCR) is defined as the percentage of participants whose best overall response is a complete response (CR), partial response (PR), or stable disease (SD), as assessed by the investigator according to RECIST v1.1.",{"measure":30,"description":31,"timeFrame":32},"Progression-Free Survival","Progression-free survival (PFS) is defined as the time from the first dose of study treatment to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.","From the first dose of study treatment until documented disease progression or death from any cause, whichever occurs first, assessed for up to approximately 24 months",{"measure":34,"description":35,"timeFrame":36},"Overall Survival","Overall survival (OS) is defined as the time from the first dose of study treatment to death from any cause.","From the first dose of study treatment until death, withdrawal of consent, loss to follow-up, or study completion, assessed for up to approximately 24 months",{"measure":38,"description":39,"timeFrame":40},"Changes in Tumor Molecular Characteristics","Tumor tissue collected at baseline and, when available according to the protocol, at disease progression will be analyzed to characterize tumor-associated molecular features and their changes over time. Exploratory analyses may include genomic, transcriptomic, or other molecular characteristics, depending on sample availability and assay feasibility.","At baseline and at documented disease progression, assessed for up to approximately 24 months",[42,46],{"measure":43,"description":44,"timeFrame":45},"Changes in Peripheral Blood Immune-Cell Characteristics","Peripheral blood samples collected at baseline and at protocol-specified time points during treatment will be analyzed to characterize changes in the immune microenvironment. Single-cell analyses will be used to assess the molecular characteristics and longitudinal changes of immune-cell populations in peripheral blood mononuclear cells, including T cells and monocyte\u002Fmyeloid-cell populations.","At baseline and at protocol-specified time points during treatment, assessed for up to approximately 24 months",{"measure":47,"description":48,"timeFrame":49},"Association of Exploratory Biomarkers With Treatment Outcomes","Exploratory tumor tissue and peripheral blood biomarkers will be evaluated for potential associations with antitumor activity and treatment-related toxicity. Antitumor activity may include tumor response and disease control according to RECIST v1.1, while toxicity may include dose-limiting toxicities and other treatment-related adverse events.","From baseline through disease progression, the end of study treatment, or study completion, assessed for up to approximately 24 months",{"allocation":51,"interventionModel":52,"interventionModelDescription":53,"primaryPurpose":54,"observationalModel":53,"timePerspective":53,"maskingInfo":55},"NA","SINGLE_GROUP",null,"TREATMENT",{"masking":56,"maskingDescription":53,"whoMasked":53},"NONE","This is a prospective, single-arm, open-label, Phase 1 dose-escalation and dose-expansion clinical trial evaluating all-trans retinoic acid (ATRA) in combination with tislelizumab in participants with advanced EGFR-mutant non-small cell lung cancer (NSCLC). The study population will include participants whose disease has progressed after a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) and at least one standard systemic therapy, as well as participants who are unable to tolerate or are considered unsuitable for currently available standard treatment. Participants must have no clearly available and appropriate standard targeted therapy, as determined by the investigator.\n\nThe study is designed to characterize the safety and tolerability of the combination, identify the maximum tolerated dose (MTD) and\u002For recommended Phase 2 dose (RP2D), and obtain preliminary evidence of antitumor activity. The study will also explore molecular and immune changes associated with treatment response and toxicity.\n\nDose Escalation and Dose Expansion\n\nA conventional 3+3 dose-escalation design will be used. Three ATRA dose levels are planned:\n\n* Dose Level 1: ATRA 30 mg orally twice daily\n* Dose Level 2: ATRA 40 mg orally twice daily\n* Dose Level 3: ATRA 50 mg orally twice daily\n\nAt each dose level, ATRA will be administered in combination with tislelizumab 200 mg by intravenous infusion once every 3 weeks. Initially, 3 participants will be enrolled at each dose level. Enrollment may be expanded to 6 participants at a dose level according to the occurrence of dose-limiting toxicities (DLTs) and the prespecified 3+3 dose-escalation rules.\n\nAfter the RP2D has been selected, approximately 6 additional participants are planned to be enrolled in a dose-expansion cohort at that dose level. The expansion cohort will provide additional information on the safety, tolerability, and preliminary antitumor activity of the combination.\n\nApproximately 15 to 24 participants are expected to be enrolled. The final sample size will depend on the number of DLTs observed and the outcome of dose escalation.\n\nTreatment Plan and DLT Evaluation\n\nTreatment will be administered in 21-day cycles. ATRA will be started 7 days before the first tislelizumab infusion. During this 7-day lead-in period, participants will receive ATRA alone. Beginning on Cycle 1 Day 1, participants will continue oral ATRA and receive tislelizumab 200 mg intravenously every 3 weeks.\n\nThe DLT evaluation period will consist of the 7-day ATRA lead-in period plus the first 21-day combination-treatment cycle, for a total of 28 days. Participants who complete the required DLT observation period, or who experience a DLT during that period, will be considered evaluable for DLT assessment.\n\nTreatment may continue according to the protocol until disease progression, unacceptable toxicity, withdrawal of consent, pregnancy, loss to follow-up, initiation of another anticancer treatment, investigator determination that continued treatment is no longer in the participant's best interest, or termination of the study.\n\nIf an adverse event considered related to ATRA occurs, supportive treatment, temporary interruption, dose reduction, or permanent discontinuation of ATRA may be used according to the type, severity, duration, and recovery of the toxicity. Dose reduction of tislelizumab is not permitted. Tislelizumab may be interrupted, resumed, or permanently discontinued for immune-related or other clinically significant adverse events in accordance with applicable prescribing information, established toxicity-management guidance, and the investigator's clinical judgment.\n\nStudy Assessments\n\nThe study includes a screening period, a 7-day ATRA lead-in period, the combination-treatment period, an end-of-treatment visit, safety follow-up, and survival follow-up.\n\nScreening assessments will generally be completed within 28 days before the first study treatment. Assessments will include medical and treatment history, physical examination, vital signs, performance status, concomitant medications, laboratory testing, electrocardiography, baseline tumor imaging, and collection of biological samples.\n\nSafety and treatment suitability will be evaluated before treatment in each 21-day cycle. Assessments will include physical examination, vital signs, body weight, performance status, hematology and blood chemistry testing, lipid testing, concomitant medication review, adverse-event monitoring, and evaluation of adherence to oral ATRA treatment.\n\nDuring the first year of treatment, tumor imaging will generally be performed every 6 weeks, with an allowed window of 7 days. After the first year, imaging may be performed every 9 weeks, with an allowed window of 7 days. Tumor response and disease progression will be assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).\n\nParticipants who discontinue all study treatment should complete an end-of-treatment visit within 28 days after the last study treatment, with an allowed window of 7 days, or before starting a new anticancer treatment, whichever occurs first. Adverse events, serious adverse events, and clinically significant laboratory abnormalities that have not resolved at treatment discontinuation will be followed until they return to baseline, improve to Grade 1 or lower, stabilize at a level considered acceptable by the investigator, are determined to be irreversible, or the participant begins a new anticancer treatment.\n\nAfter completion of safety follow-up, survival status and information about subsequent anticancer treatment will be collected approximately every 3 months, with an allowed window of 7 days, until death, loss to follow-up, withdrawal of consent, or study termination.\n\nTranslational and Biomarker Research\n\nTumor tissue will be collected at baseline and, when specified by the protocol, at disease progression. Peripheral blood will be collected at baseline and at planned time points during treatment. These samples will be used to characterize tumor-associated molecular features and their changes over time.\n\nSingle-cell analyses may be used to evaluate the molecular characteristics and longitudinal changes of immune-cell populations in peripheral blood mononuclear cells, including T cells and monocyte\u002Fmyeloid-cell populations. These exploratory analyses are intended to identify potential biomarkers associated with antitumor activity or treatment-related toxicity and to generate hypotheses regarding possible predictors of treatment response.\n\nStatistical Considerations\n\nNo formal statistical hypothesis testing is planned for this Phase 1 dose-finding study. Analyses will primarily be descriptive. Safety findings and DLTs will be summarized overall and by dose level. Selection of the MTD and\u002For RP2D will be based on the prespecified 3+3 dose-escalation rules together with the overall available safety, tolerability, and clinical data.\n\nPreliminary antitumor activity will be summarized descriptively. Time-to-event measures may be explored using the Kaplan-Meier method if the available data are sufficiently mature. Biomarker analyses will be exploratory and will be conducted in participants with suitable tumor tissue or peripheral blood samples and the corresponding clinical data.",[59],{"label":60,"type":61,"description":62,"interventionNames":63},"Experimental: All-Trans Retinoic Acid Plus Tislelizumab","EXPERIMENTAL","Participants will receive oral all-trans retinoic acid (ATRA) at the assigned dose level of 30 mg, 40 mg, or 50 mg twice daily in combination with tislelizumab 200 mg administered by intravenous infusion once every 3 weeks.\n\nATRA will begin 7 days before the first tislelizumab infusion as an ATRA lead-in period and will then continue during the 21-day combination-treatment cycles. The dose-escalation phase will follow a conventional 3+3 design. After the recommended dose for further study has been determined, additional participants will receive the combination at that dose in a dose-expansion cohort.\n\nThe dose-limiting toxicity evaluation period will include the 7-day ATRA lead-in period and the first 21-day combination-treatment cycle, for a total of 28 days. Treatment may continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of another anticancer treatment, investigator decision, or another protocol-defined discontinuation criterion.",[64,65],"Drug: All-trans retinoic acid","Drug: Tislelizumab",[67,72],{"type":68,"name":69,"description":70,"armGroupLabels":71,"otherNames":53},"DRUG","All-trans retinoic acid","All-trans retinoic acid will be administered orally twice daily at an assigned dose level of 30 mg, 40 mg, or 50 mg. ATRA will begin 7 days before the first tislelizumab infusion and will continue during the subsequent 21-day combination-treatment cycles. Dose escalation will follow a conventional 3+3 design. After the recommended dose for further study has been determined, additional participants will receive ATRA at that dose in the dose-expansion cohort. ATRA may be interrupted, reduced, or permanently discontinued according to the type, severity, duration, and recovery of treatment-related toxicity.",[60],{"type":68,"name":73,"description":74,"armGroupLabels":75,"otherNames":53},"Tislelizumab","Tislelizumab, a programmed cell death protein 1 (PD-1) inhibitor, will be administered at a dose of 200 mg by intravenous infusion once every 3 weeks. The first dose will be administered after the 7-day ATRA lead-in period, and tislelizumab will then be given in combination with oral ATRA during each 21-day treatment cycle. Dose reduction of tislelizumab is not permitted. Treatment may be interrupted, resumed, or permanently discontinued for immune-related or other clinically significant adverse events according to applicable prescribing information, established toxicity-management guidance, and the investigator's clinical judgment.",[60],[77],{"name":78,"role":79,"phone":80,"phoneExt":53,"email":81},"Zhijie Wang Jiachen Xu, MD","CONTACT","+86 13466323860","jie_969@163.com",[83],{"facility":84,"status":53,"city":85,"state":86,"zip":87,"country":88,"countryCode":89,"cosmosGeoPoint":90,"geoPoint":95,"contacts":96},"National Cancer Center\u002FNational Clinical Research Center for Cancer\u002FCancer Hospital","Beijing","Beijing Municipality","100021","China","CN",{"type":91,"coordinates":92},"Point",[93,94],116.39723,39.9075,{"lat":94,"lon":93},[97,99],{"name":98,"role":79,"phone":53,"phoneExt":53,"email":81},"National Cancer Center National Clinical Research Center",{"name":53,"role":79,"phone":53,"phoneExt":53,"email":81},{"type":101,"investigatorFullName":102,"investigatorTitle":103,"investigatorAffiliation":5,"oldNameTitle":53,"oldOrganization":53},"PRINCIPAL_INVESTIGATOR","Zhijie Wang","Chief Physician","100657645","phase-1-phase-1-study-of-atra-plus-a-pd-1-inhibitor-in-egfr-mutant-nsclc-after-third-generation-egfr-tki-resistance-100657645",false,"NCT07842887","Phase 1 Study of ATRA Plus a PD-1 Inhibitor in EGFR-Mutant NSCLC After Third-Generation EGFR-TKI Resistance","A Phase 1 Clinical Study of All-Trans Retinoic Acid in Combination With a PD-1 Inhibitor in Patients With EGFR-Mutant Non-Small Cell Lung Cancer After Acquired Resistance to a Third-Generation EGFR Tyrosine Kinase Inhibitor","A Phase 1 Clin","Inclusion Criteria:\n\n1. Voluntarily provides written informed consent and agrees to comply with the study requirements.\n2. Aged 18 years or older, with no restriction based on sex.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants with an ECOG performance status of 2 may be enrolled at the investigator's discretion.\n4. Histologically or pathologically confirmed primary non-small cell lung cancer (NSCLC).\n5. Stage IV disease according to the eighth edition of the American Joint Committee on Cancer\u002FUnion for International Cancer Control TNM staging system, or recurrent or metastatic NSCLC that is not suitable for curative local treatment.\n6. A confirmed sensitizing EGFR mutation, including but not limited to an exon 19 deletion or an exon 21 L858R mutation.\n7. Previous treatment with a third-generation EGFR tyrosine kinase inhibitor, including but not limited to osimertinib, almonertinib, or furmonertinib, followed by radiographically confirmed disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).\n8. Disease progression after at least one standard systemic treatment following resistance to a third-generation EGFR tyrosine kinase inhibitor, or inability to tolerate or unsuitability for currently available standard treatment, as determined by the investigator.\n9. No clearly available and appropriate standard targeted therapy option, as determined by the investigator.\n10. At least one measurable lesion according to RECIST v1.1.\n11. Adequate major organ function to receive the study treatment, as determined by the investigator.\n12. Female participants of childbearing potential must have a negative pregnancy test and agree to use effective contraception during study treatment and for at least 1 month after the last dose of all-trans retinoic acid.\n13. Able to understand and comply with the study requirements, as determined by the investigator.\n\nExclusion Criteria:\n\n1. History of another malignancy, except for a malignancy that has been clinically cured and is considered by the investigator to have a low risk of recurrence.\n2. Uncontrolled brain metastases, leptomeningeal metastases, or a central nervous system lesion requiring urgent local treatment.\n3. Histologic transformation, such as transformation to small cell lung cancer.\n4. Uncontrolled acute or chronic infection, or an active infection requiring systemic anti-infective treatment.\n5. Active tuberculosis.\n6. Positive human immunodeficiency virus antibody test, active hepatitis B, or active hepatitis C.\n7. Active autoimmune disease, or a history of autoimmune disease requiring systemic immunosuppressive treatment.\n8. A history of a Grade 3 or higher immune-related adverse event following treatment with an immune checkpoint inhibitor, or permanent discontinuation of immunotherapy because of immune-related toxicity.\n9. Severe or uncontrolled cardiovascular or cerebrovascular disease.\n10. An unstable thrombotic or bleeding event requiring therapeutic intervention within 6 months before screening.\n11. Clinically significant uncontrolled hyperlipidemia, particularly markedly elevated triglycerides, that may increase the risks associated with all-trans retinoic acid treatment, as determined by the investigator.\n12. Uncontrolled Grade 2 or higher hepatic dysfunction, or underlying liver disease that may substantially increase the risk of ATRA-related hepatotoxicity, as determined by the investigator.\n13. History of a severe hypersensitivity reaction to all-trans retinoic acid, another retinoid, tislelizumab, or any component of these products.\n14. Pregnant or breastfeeding, or planning pregnancy or conception during the study.\n15. Previous or current benign intracranial hypertension or pseudotumor cerebri.\n16. Current treatment with a tetracycline that cannot be discontinued.\n17. Current treatment with another anticancer therapy or investigational product without completion of the protocol-required washout period.\n18. Any other condition that, in the investigator's opinion, makes the individual unsuitable for participation in the clinical trial.","ALL","18 Years",{"count":115,"type":116},24,"ESTIMATED","INTERVENTIONAL",[119],"PHASE1","The goal of this Phase 1 clinical trial is to learn whether all-trans retinoic acid (ATRA) combined with tislelizumab is safe and tolerable in adults with EGFR-mutant non-small cell lung cancer (NSCLC). The study is for people whose cancer has worsened after treatment with a third-generation EGFR tyrosine kinase inhibitor and at least one standard systemic treatment, or who cannot tolerate or are not suitable for currently available standard treatments.\n\nThe main questions this study aims to answer are:\n\n* What side effects and dose-limiting toxicities occur with the combination of ATRA and tislelizumab?\n* What is the highest dose of ATRA that can be given safely with tislelizumab, and what dose should be recommended for future studies?\n\nResearchers will also look for early signs that the combination can shrink or control the cancer and will assess how long participants live without their cancer getting worse and how long they live overall. Tumor tissue and blood samples will be studied to explore changes in the cancer and the immune system and to identify possible markers associated with treatment response or side effects.\n\nAll participants will receive ATRA and tislelizumab; there is no comparison or placebo group. Participants will:\n\n* Take ATRA by mouth twice daily, beginning 7 days before the first dose of tislelizumab. The ATRA dose will be assigned according to the dose level being studied.\n* Receive tislelizumab by intravenous infusion once every 3 weeks.\n* Undergo regular safety assessments, including physical examinations, blood tests, vital-sign measurements, and monitoring for side effects.\n* Undergo imaging examinations approximately every 6 weeks during the first year to assess the cancer.\n* Provide tumor tissue and blood samples for biomarker research.\n* Attend an end-of-treatment visit, safety follow-up visits, and survival follow-up approximately every 3 months after treatment ends.",[122],"EGFR-TKI-resistant Non-Small Cell Lung Cancer",[124,125,126,127,128,129],"Third-Generation EGFR Tyrosine Kinase Inhibitor Resistance","Acquired Drug Resistance","Programmed Cell Death 1 Inhibitor","Dose Escalation","Tumor Immune Microenvironment","Predictive Biomarkers","NOT_YET_RECRUITING","2026-09-21",{"date":133,"type":134},"2026-09-25","ACTUAL",{"date":136,"type":116},"2026-10-01",{"date":138,"type":116},"2028-10-10",{"name":5,"class":6},1]