[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Beijing Biotech\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":721},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,31,0,25,[9,57,90,122,151,179,206,236,258,284,304,327,352,377,404,425,469,498,542,569,593,613,644,668,697],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":16,"eligibilityCriteria":17,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":21,"targetDuration":4,"studyType":24,"phases":25,"briefSummary":28,"conditions":29,"keywords":32,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":45,"lastUpdatePostDateStruct":46,"startDateStruct":49,"completionDateStruct":51,"leadSponsor":53,"locationsCount":56},"100643105","phase-1-dual-target-car-nk-cells-targeting-msln-egfr-or-her2-in-advanced-nsclc-100643105",false,"NCT07641023","Dual-Target CAR-NK Cells Targeting MSLN, EGFR, or HER2 in Advanced NSCLC","A Phase 1\u002F2, Open-label, Biomarker-guided Study of Dual-target Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Targeting Mesothelin (MSLN) With EGFR or HER2\u002FERBB2, or EGFR With HER2\u002FERBB2, in Participants With Advanced\u002FMetastatic Non-small Cell Lung Cancer (NSCLC)","DUO-NK-NSCLC","Inclusion Criteria:\n\n* Histologically or cytologically confirmed NSCLC that is unresectable Stage IIIB\u002FIIIC or Stage IV, with radiographic progression on or after standard-of-care therapy (including platinum-based chemotherapy and immune checkpoint inhibitor when appropriate).\n* At least one measurable lesion per RECIST v1.1.\n* Archival tumor tissue available (or willingness to undergo a fresh biopsy) for antigen testing.\n* Tumor co-expression of at least two of the following antigens at screening: MSLN, EGFR, HER2\u002FERBB2.\n\nExample thresholds: IHC ≥2+ in ≥50% of tumor cells for each required antigen (or an equivalent RNA expression threshold).\n\n* ECOG performance status 0-1.\n* Adequate organ function (hematologic, hepatic, renal) as defined by protocol laboratory limits.\n* Life expectancy ≥12 weeks.\n* Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception for the study-defined period.\n* Ability to understand and willingness to sign written informed consent.\n\nExclusion Criteria:\n\n* Active, uncontrolled central nervous system (CNS) metastases. Participants with previously treated\u002Fstable CNS disease may be eligible if clinically stable and off high-dose corticosteroids.\n* Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK, TCR-T) within 3 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.\n* History of severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior therapies.\n* Clinically significant interstitial lung disease or pneumonitis requiring systemic steroids, or uncontrolled pulmonary comorbidity that would confound toxicity monitoring.\n* Active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).\n* Active uncontrolled infection, including uncontrolled HIV, active hepatitis B, or active hepatitis C infection.\n* Significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or LVEF below institutional lower limit).\n* Pregnant or breastfeeding.\n* Concurrent anti-cancer therapy (chemotherapy, targeted therapy, immunotherapy) within protocol-defined washout periods.\n* Any condition that, in the investigator's opinion, would interfere with participant safety or compliance","ALL","18 Years","75 Years",{"count":22,"type":23},60,"ESTIMATED","INTERVENTIONAL",[26,27],"PHASE1","PHASE2","This is a two-part, biomarker-guided Phase 1\u002F2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and HER2\u002FERBB2.\n\nParticipants will receive lymphodepleting chemotherapy followed by infusion of the CAR-NK product matched to their tumor antigen profile. A data-driven interim assessment will be used to select the most suitable construct for expansion.",[30,31],"Non-Small Cell Lung Cancer","Advanced\u002FMetastatic",[33,34,35,36,37,38,39,40,41,42,43],"CAR-NK","Dual-target","Bispecific","Adoptive cell therapy","Solid tumor","Immunotherapy","Biomarker-guided","Mesothelin","EGFR","HER2","Dose escalation","RECRUITING","2026-06-06",{"date":47,"type":48},"2026-06-11","ACTUAL",{"date":50,"type":48},"2026-03-02",{"date":52,"type":23},"2028-06-17",{"name":54,"class":55},"Beijing Biotech","INDUSTRY",1,{"id":58,"slug":59,"hasResults":12,"nctId":60,"briefTitle":61,"officialTitle":62,"acronym":63,"eligibilityCriteria":64,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":65,"targetDuration":4,"studyType":24,"phases":67,"briefSummary":68,"conditions":69,"keywords":75,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":45,"lastUpdatePostDateStruct":85,"startDateStruct":86,"completionDateStruct":87,"leadSponsor":89,"locationsCount":56},"100642684","phase-1-dual-target-her2cea-car-nk-cells-in-advanced-biliary-tract-cancer-100642684","NCT07641036","Dual-Target HER2\u002FCEA CAR-NK Cells in Advanced Biliary Tract Cancer","A Phase 1\u002F2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target HER2\u002FCEACAM5 Chimeric Antigen Receptor Natural Killer Cells (EB-HC01) in Participants With Unresectable or Metastatic Cholangiocarcinoma and Other Biliary Tract Cancers","DUET-BTC","Inclusion Criteria:\n\n* Histologically or cytologically confirmed unresectable, recurrent, or metastatic intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma.\n* Disease progression after at least 1 prior gemcitabine\u002Fplatinum-containing regimen in the advanced setting; prior durvalumab and prior HER2-targeted therapy are allowed.\n* Central biomarker confirmation of HER2 positivity (IHC 3+ or IHC 2+\u002FISH+ or ERBB2 amplification) and CEACAM5\u002FCEA positivity (membranous expression in \\>=20% of viable tumor cells by IHC).\n* At least 1 measurable lesion according to RECIST 1.1.\n* ECOG performance status 0-1.\n* Adequate marrow, renal, hepatic, and cardiac function as defined by the protocol.\n* Resolved biliary obstruction or stable internal\u002Fexternal drainage for \\>=7 days before lymphodepletion, with no active cholangitis.\n* Life expectancy \\>=12 weeks.\n* Willingness to provide archival or fresh tumor tissue and serial blood samples for central biomarker testing and correlative studies.\n* Agreement to use protocol-specified contraception\n\nExclusion Criteria:\n\n* Prior HER2-directed or CEA-directed gene-modified cell therapy.\n* Untreated or unstable CNS metastases or leptomeningeal disease.\n* Active uncontrolled infection, including uncontrolled cholangitis, sepsis, or clinically significant uncontrolled hepatitis or HIV infection.\n* Ongoing systemic immunosuppression greater than 10 mg\u002Fday prednisone equivalent within 7 days before lymphodepletion.\n* Clinically significant interstitial lung disease, uncontrolled heart failure, unstable arrhythmia, or recent myocardial infarction.\n* Child-Pugh B or C liver disease, hepatic encephalopathy, or clinically significant refractory ascites.\n* Prior allogeneic solid organ transplant or allogeneic stemcell transplant.\n* Active autoimmune disease requiring systemic therapy within the previous 2 years.\n* Pregnancy or breastfeeding.\n* Any condition that, in the investigator's judgment, would make lymphodepletion or EB-HC01 infusion unsafe or would interfere with protocol compliance.",{"count":66,"type":23},30,[26,27],"This example phase 1\u002F2, open-label, biomarker-selected study evaluates EB-HC01, an allogeneic dual-target CARNK product composed of a 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells, in adults with unresectable or metastatic cholangiocarcinoma or other biliary tract cancers after standard therapy. Part A determines safety, dose-limiting toxicities (DLTs), and the recommended phase 2 dose (RP2D) after reduced-intensity lymphodepletion. Part B evaluates preliminary anti-tumor activity, CAR-NK persistence, and biomarker-response associations.",[70,71,72,73,74],"Cholangiocarcinoma","Intrahepatic Cholangiocarcinoma","Extrahepatic Cholangiocarcinoma","Gallbladder Carcinoma","Biliary Tract Cancer",[33,76,42,77,78,79,80,81,82,83,84],"dual-target cell therapy","ERBB2","CEA","CEACAM5","cholangiocarcinoma","biliary tract cancer","allogeneic","off-the-shelf","adoptive cell therapy",{"date":47,"type":48},{"date":50,"type":48},{"date":88,"type":23},"2028-10-17",{"name":54,"class":55},{"id":91,"slug":92,"hasResults":12,"nctId":93,"briefTitle":94,"officialTitle":95,"acronym":96,"eligibilityCriteria":97,"healthyVolunteers":12,"sex":98,"minAge":19,"maxAge":4,"enrollmentInfo":99,"targetDuration":4,"studyType":24,"phases":101,"briefSummary":102,"conditions":103,"keywords":108,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":45,"lastUpdatePostDateStruct":118,"startDateStruct":119,"completionDateStruct":120,"leadSponsor":121,"locationsCount":56},"100643460","phase-1-dual-target-psmapsca-car-nk-cells-in-advanced-prostate-cancer-100643460","NCT07641049","Dual-target PSMA\u002FPSCA CAR-NK Cells in Advanced Prostate Cancer","A Phase 1, Open-Label, Multicenter, Dose-Escalation and Dose-Expansion Study of ETB-DualNK-01, an Allogeneic Dual-target PSMA\u002FPSCA CAR-NK Cell Product, in Adults With Metastatic Castration-Resistant Prostate Cancer","DUAL-NK-PC","Inclusion Criteria:\n\n* Male participant age 18 years or older.\n* Histologically or cytologically confirmed prostate adenocarcinoma with metastatic castration-resistant disease.\n* Disease progression by PCWG3 while maintaining castrate testosterone (\\\u003C50 ng\u002FdL) with ongoing androgen deprivation therapy or prior orchiectomy.\n* Documented PSMA and\u002For PSCA expression by a validated tumor assay; PSMA PET may support target confirmation when applicable.\n* Prior progression on at least one androgen receptor pathway inhibitor such as abiraterone, enzalutamide, apalutamide, or darolutamide; prior taxane, PARP inhibitor, radioligand therapy, or checkpoint inhibitor is allowed.\n* ECOG performance status 0 or 1.\n* Adequate hematologic, renal, hepatic, cardiac, and pulmonary function per protocol laboratory thresholds.\n* At least one measurable lesion by RECIST 1.1 or evaluable bone-predominant disease by PCWG3.\n* Life expectancy of at least 12 weeks.\n* Ability to understand and sign informed consent and willingness to provide required blood and tissue samples.\n\nExclusion Criteria:\n\n* Active central nervous system metastases or leptomeningeal disease.\n* Dominant small-cell or neuroendocrine prostate cancer histology.\n* Prior gene-modified cellular therapy within 6 months before lymphodepletion, or prior allogeneic transplant requiring ongoing systemic immunosuppression.\n* Active autoimmune disease requiring systemic treatment or chronic immunosuppression; systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days of lymphodepletion.\n* Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.\n* Clinically significant cardiovascular disease, symptomatic arrhythmia, recent myocardial infarction, or uncontrolled heart failure.\n* Unresolved grade 2 or higher toxicity from prior anticancer therapy, except alopecia, stable endocrinopathy, or other protocol-approved exceptions.\n* Another active malignancy requiring systemic treatment.\n* Any medical, psychiatric, or laboratory abnormality that, in the investigator's judgment, would increase risk or interfere with study interpretation.","MALE",{"count":100,"type":23},36,[26],"This example Phase 1 study is designed to evaluate the safety, tolerability, feasibility, and preliminary anti-tumor activity of ETB-DualNK-01, an allogeneic dual-target PSMA\u002FPSCA CAR-NK cell therapy, in adults with metastatic castration-resistant prostate cancer (mCRPC). Part A uses dose escalation to determine the maximum tolerated dose and\u002For recommended Phase 2 dose. Part B expands at the selected dose in biomarkerconfirmed disease.",[104,105,106,107],"Metastatic Castration-resistant Prostate Cancer","Advanced Prostate Adenocarcinoma","PSCA-positive Prostate Cancer","PSMA-Positive Progressive Metastatic Castration-Resistant Prostate Cancer",[33,109,110,111,112,113,114,115,116,117],"dual-target","PSMA","PSCA","mCRPC","metastatic prostate cancer","cell therapy","immunotherapy","dose escalation","dose expansion",{"date":47,"type":48},{"date":50,"type":48},{"date":52,"type":23},{"name":54,"class":55},{"id":123,"slug":124,"hasResults":12,"nctId":125,"briefTitle":126,"officialTitle":127,"acronym":128,"eligibilityCriteria":129,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":130,"targetDuration":4,"studyType":24,"phases":131,"briefSummary":132,"conditions":133,"keywords":137,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":145,"lastUpdatePostDateStruct":146,"startDateStruct":148,"completionDateStruct":149,"leadSponsor":150,"locationsCount":56},"100641091","phase-1-dual-target-cspg4gd2-car-nk-cells-for-advanced-melanoma-100641091","NCT07627698","Dual-Target CSPG4\u002FGD2 CAR-NK Cells for Advanced Melanoma","An Open-Label, Multicenter Phase 1\u002F2 Study of Allogeneic Dual-Target CSPG4\u002FGD2 CAR-NK Cells (EB-DTKN-401) in Adults With Unresectable or Metastatic Cutaneous Melanoma or Metastatic Uveal Melanoma","DUET-MEL","Inclusion Criteria:\n\n* Age 18-75 years at consent.\n* Histologically confirmed unresectable\u002Fmetastatic cutaneous melanoma or metastatic uveal melanoma.\n* Disease progression after standard therapy, intolerance to standard therapy, or no remaining standard option expected to provide meaningful benefit. For cutaneous melanoma: prior anti-PD-1\u002FL1 (with or without antiCTLA-4) unless contraindicated; if BRAF V600-mutant, prior BRAF\u002FMEK inhibitor therapy or documented unsuitability. For uveal melanoma: prior tebentafusp if HLA-A\\*02:01-positive and eligible, or documented unsuitability\u002Funavailability plus at least one prior systemic therapy.\n* Tumor demonstrates CSPG4 and\u002For GD2 expression in archival or fresh tissue by central testing (suggested positivity threshold: at least 25% viable tumor cells by IHC or equivalent validated assay).\n* At least 1 measurable lesion by RECIST v1.1.\n* ECOG performance status 0-1.\n* Adequate bone marrow, renal, hepatic, cardiac, and pulmonary function per protocol.\n* Life expectancy of at least 12 weeks.\n* Treated, stable brain metastases are allowed if neurologically stable for at least 4 weeks and not requiring escalating corticosteroids.\n* Willingness to use effective contraception and comply with protocol-required visits, blood sampling, and requested biopsies.\n\nExclusion Criteria:\n\n* Active symptomatic CNS metastases, leptomeningeal disease, or uncontrolled seizure disorder.\n* Prior allogeneic stem cell transplant or solid organ transplant; prior gene-modified cellular therapy within 12 weeks; or anti-cancer therapy too close to lymphodepletion per protocol washout rules.\n* Requirement for systemic immunosuppression greater than 10 mg prednisone equivalent\u002Fday or uncontrolled autoimmune\u002Finflammatory disease requiring systemic treatment.\n* Active uncontrolled infection, including uncontrolled HIV, HBV, or HCV, or fever\u002Fsepsis at the time lymphodepletion would begin.\n* Clinically significant cardiovascular disease, uncontrolled arrhythmia, recent myocardial infarction, or uncontrolled thromboembolic disease.\n* Grade 2 or higher unresolved toxicities from prior therapy, except stable endocrinopathy, alopecia, or vitiligo.\n* Pregnancy or breastfeeding.\n* Any condition that, in the investigator's judgment, would make lymphodepletion or CAR-NK infusion unsafe.",{"count":100,"type":23},[26,27],"This is a first-in-human, open-label, multicenter phase 1\u002F2 study evaluating the safety, feasibility, recommended phase 2 dose (RP2D), and preliminary antitumor activity of allogeneic dual-target CSPG4\u002FGD2 CAR-NK cells (EBDTKN-401) after lymphodepleting chemotherapy in adults with unresectable or metastatic cutaneous melanoma or metastatic uveal melanoma whose disease has progressed after standard therapy",[134,135,136],"Unresectable Melanoma","Metastatic Cutaneous Melanoma","Metastatic Uveal Melanoma",[33,138,139,140,141,142,114,143,144],"allogeneic NK cells","CSPG4","GD2","advanced melanoma","uveal melanoma","biomarker-guided","solid tumor","2026-05-31",{"date":147,"type":48},"2026-06-04",{"date":50,"type":48},{"date":52,"type":23},{"name":54,"class":55},{"id":152,"slug":153,"hasResults":12,"nctId":154,"briefTitle":155,"officialTitle":156,"acronym":4,"eligibilityCriteria":157,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":158,"targetDuration":4,"studyType":24,"phases":159,"briefSummary":160,"conditions":161,"keywords":164,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":145,"lastUpdatePostDateStruct":173,"startDateStruct":175,"completionDateStruct":176,"leadSponsor":178,"locationsCount":56},"100638606","phase-1-dual-target-cldn182her2-car-nk-cells-for-advanced-esophageal-adenocarcinoma-100638606","NCT07622940","Dual-Target CLDN18.2\u002FHER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma","A Phase 1\u002F2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target CLDN18.2\u002FHER2 Chimeric Antigen Receptor Natural Killer Cells (EBNK-1822H2) in Adults With Relapsed, Refractory, or Metastatic Esophageal Adenocarcinoma","Inclusion Criteria:\n\n* Histologically confirmed esophageal adenocarcinoma or Siewert I\u002FII gastroesophageal junction adenocarcinoma judged biologically consistent with esophageal adenocarcinoma, unresectable\u002Frecurrent\u002Fmetastatic, and not amenable to curative therapy.\n* Disease progressed after at least 1 prior systemic regimen for advanced disease, or the participant is intolerant of \u002F ineligible for standard therapy. Biomarker-directed therapy must have been received or deemed inappropriate\u002Funavailable where standard in the local setting.\n* At least 1 measurable lesion by RECIST v1.1.\n* Evidence of at least one selected target: CLDN18.2-positive by validated IHC (example threshold: membranous staining in\n\n  ≥75% of tumor cells with moderate\u002Fstrong intensity or protocol-specified central threshold), and\u002For HER2-positive by IHC 3+ or IHC 2+\u002FISH-amplified disease.\n* ECOG performance status 0-1.\n* Adequate marrow, renal, hepatic, pulmonary, and cardiac function per protocol laboratory thresholds.\n* Life expectancy ≥12 weeks.\n* Resolution of clinically significant prior-therapy toxicities to grade ≤1 (except alopecia or stable endocrinopathies).\n* Willingness to provide archival tumor tissue and to undergo fresh biopsy when safely feasible.\n* Negative pregnancy test for participants of childbearing potential and agreement to protocol-defined contraception.\n\nExclusion Criteria:\n\n* Esophageal squamous cell carcinoma or non-adenocarcinoma histology.\n* Known active CNS metastases or leptomeningeal disease; previously treated stable CNS disease may be allowed only if asymptomatic and off escalating steroids per protocol.\n* Prior gene-modified cellular therapy within 12 weeks, or another investigational therapy likely to confound interpretation of safety or efficacy.\n* Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV viremia, sepsis, or clinically significant opportunistic infection.\n* Ongoing systemic immunosuppressive therapy above physiologic steroid replacement.\n* Active autoimmune disease requiring systemic treatment within 2 years.\n* Clinically significant interstitial lung disease\u002Fpneumonitis, uncontrolled cardiovascular disease, or left ventricular ejection fraction \\\u003C50%.\n* Active gastrointestinal perforation, uncontrolled bleeding, or clinically significant mucosal ulceration that would increase study-treatment risk.\n* Prior solid organ transplant or active graft-versus-host disease.\n* Pregnant or breastfeeding.\n* Another active malignancy requiring systemic therapy, except protocol-permitted low-risk cancers.",{"count":100,"type":23},[26,27],"This example study evaluates the safety, feasibility, cellular kinetics, and preliminary anti-tumor activity of EBNK-1822H2, an illustrative allogeneic cord blood-derived dual-target CAR-NK cell product directed against CLDN18.2 and HER2, in adults with relapsed\u002Frefractory or metastatic esophageal adenocarcinoma after standard therapy. The study uses dose escalation followed by biomarker-defined expansion and prospectively records EGFR expression as an exploratory biomarker of antigen escape.",[162,163],"Recurrent or Metastatic Esophageal Adenocarcinoma","Biomarker-selected CLDN18.2-positive and\u002For HER2-positive Disease",[33,165,166,167,168,169,170,171,43,172],"Allogeneic NK cells","Cellular immunotherapy","CLDN18.2","HER2 (ERBB2)","EGFR (exploratory biomarker)","Esophageal adenocarcinoma","Gastroesophageal junction adenocarcinoma","Dose expansion",{"date":174,"type":48},"2026-06-03",{"date":50,"type":48},{"date":177,"type":23},"2028-03-17",{"name":54,"class":55},{"id":180,"slug":181,"hasResults":12,"nctId":182,"briefTitle":183,"officialTitle":184,"acronym":185,"eligibilityCriteria":186,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":187,"targetDuration":4,"studyType":24,"phases":189,"briefSummary":190,"conditions":191,"keywords":195,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":145,"lastUpdatePostDateStruct":202,"startDateStruct":203,"completionDateStruct":204,"leadSponsor":205,"locationsCount":56},"100637483","phase-1-dual-target-car-nk-cells-targeting-mesothelin-msln-and-muc1-in-advanced-pancreatic-ductal-adenocarcinoma-100637483","NCT07627711","Dual-Target CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma","A Phase 1\u002F2, Open-label, Biomarker-guided, Dose-escalation and Expansion Study of Dual-targeting CAR-NK Cells Directed Against Mesothelin (MSLN) and MUC1, With an Exploratory CLDN18.2\u002FMUC1 Dual-target Cohort, in Patients With Unresectable or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)","DUAL-NK-PDAC","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC).\n* Unresectable locally advanced or metastatic disease with progression after at least 1 prior standard systemic therapy regimen, or intolerance\u002Fineligibility for standard therapy.\n* At least 1 measurable lesion per RECIST v1.1.\n* Tumor antigen expression by central IHC (archival or fresh biopsy): • Arm A eligibility: MSLN positive and\u002For MUC1 positive. • Arm B eligibility: CLDN18.2 positive and\u002For MUC1 positive. (Example threshold: IHC 2+ or 3+ staining in \\>=50% of tumor cells, or H-score above protocol-defined cutoff.)\n* ECOG performance status 0-1.\n* Adequate organ function (example): ANC \\>= 1.0 x 10\\^9\u002FL; platelets \\>= 75 x 10\\^9\u002FL; hemoglobin \\>= 8 g\u002FdL; AST\u002FALT \\\u003C= 3x ULN (\\\u003C= 5x ULN with liver metastases); total bilirubin \\\u003C= 1.5x ULN; creatinine clearance \\>= 50 mL\u002Fmin.\n* Life expectancy \\>= 12 weeks.\n* Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined follow-up period.\n* Ability to understand and willingness to sign written informed consent.\n\nExclusion Criteria:\n\n* Active or untreated CNS metastases or carcinomatous meningitis.\n* Clinically significant uncontrolled infection (including uncontrolled bacterial, fungal, or viral infection).\n* Known active hepatitis B or hepatitis C with detectable viral load; known uncontrolled HIV infection.\n* Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.\n* Prior gene-modified cellular therapy (e.g., CAR-T\u002FCAR-NK) within 6 months or prior therapy targeting the same antigen(s) Ongoing requirement for systemic immunosuppressive therapy (e.g., chronic corticosteroids above physiologic replacement).\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, or NYHA class III\u002FIV heart failure) within a protocol-defined period.\n* Active autoimmune disease requiring systemic treatment in the past 2 years (replacement therapy allowed).\n* Pregnant or breastfeeding.\n* Any medical, psychiatric, or social condition that, in the investigator's opinion, would interfere with safe participation or interpretation of results.",{"count":188,"type":23},42,[26,27],"This example study evaluates the safety, tolerability, and preliminary anti-tumor activity of investigational, dual-targeting chimeric antigen receptor natural killer (CAR-NK) cell products for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Participants are assigned to one of two biomarker-defined cohorts based on tumor antigen expression: (A) Mesothelin (MSLN) and\u002For MUC1, or (B) Claudin 18.2 (CLDN18.2) and\u002For MUC1. The study uses a dose-escalation followed by dose-expansion design to define a recommended Phase 2 dose (RP2D) and to estimate response rates in each cohort.",[192,193,194],"Pancreatic Ductal Adenocarcinoma (PDAC)","Unresectable Locally Advanced","Metastatic Disease",[196,197,33,198,40,199,200,201,167,36,38,39],"Pancreatic cancer","PDAC","Natural killer cells","MSLN","MUC1","Claudin 18.2",{"date":147,"type":48},{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":207,"slug":208,"hasResults":12,"nctId":209,"briefTitle":210,"officialTitle":211,"acronym":212,"eligibilityCriteria":213,"healthyVolunteers":12,"sex":214,"minAge":19,"maxAge":20,"enrollmentInfo":215,"targetDuration":4,"studyType":24,"phases":216,"briefSummary":217,"conditions":218,"keywords":223,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":230,"lastUpdatePostDateStruct":231,"startDateStruct":233,"completionDateStruct":234,"leadSponsor":235,"locationsCount":56},"100639206","phase-1-dual-targeting-car-nk-cells-for-recurrent-ovarian-cancer-msln-fr-muc16-pt2-100639206","NCT07617753","Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16) pt2","A Phase 1\u002F2, Open-Label, Biomarker-Assigned Study of Dual-Targeting CAR-NK Cells Directed Against Mesothelin (MSLN), Folate Receptor Alpha (FRα\u002FFOLR1), and\u002For MUC16 (CA125) in Patients With Recurrent or Refractory High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer","DUAL-OV-CAR-NK","Inclusion Criteria:\n\n* Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (high-grade serous preferred).\n* Recurrent or refractory disease after at least 2 prior systemic treatment lines (including a platinum-based regimen unless contraindicated).\n* Measurable disease per RECIST v1.1.\n* Tumor expresses at least two of the following targets above protocol-defined threshold: MSLN, FRalpha (FOLR1), MUC16 (CA 125) (archival or fresh biopsy).\n* ECOG performance status 0-1.\n* Adequate organ function : ANC \\>= 1.0 x 10\\^9\u002FL; platelets \\>= 75 x 10\\^9\u002FL; hemoglobin \\>= 8 g\u002FdL; AST\u002FALT \\\u003C= 3 x ULN (\\\u003C= 5 x ULN with liver metastases); total bilirubin \\\u003C= 1.5 x ULN; creatinine clearance \\>= 50 mL\u002Fmin.\n* Negative pregnancy test for women of childbearing potential; agreement to use effective contraception through 12 months post-infusion (or per local gene-therapy guidance).\n* Able to comply with study procedures and follow-up schedule; written informed consent.\n\nExclusion Criteria:\n\n* Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 6 months (or any prior therapy directed to the same target, per protocol).\n* Active central nervous system (CNS) metastases or carcinomatous meningitis requiring therapy.\n* Uncontrolled infection, including active tuberculosis; or clinically significant, uncontrolled viral infection.\n* Known HIV infection with uncontrolled viremia; active hepatitis B or hepatitis C with detectable viral load (testing required at screening).\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, NYHA Class III\u002FIV heart failure).\n* Active autoimmune disease requiring systemic immunosuppression within 30 days (physiologic steroid replacement allowed).\n* Concurrent anti-cancer therapy (chemotherapy, targeted therapy, radiotherapy) not permitted within a protocol-defined washout period.\n* Major surgery within 4 weeks prior to lymphodepletion (except minor procedures)\n* Pregnant or breastfeeding.\n* Any condition that, in the investigator's judgment, would increase risk (e.g., severe pulmonary disease) or interfere with study interpretation.","FEMALE",{"count":100,"type":23},[26,27],"This Phase 1\u002F2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in participants with recurrent or refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer. At screening, each participant's tumor is assessed for expression of Mesothelin (MSLN), Folate Receptor alpha (FRalpha\u002FFOLR1), and MUC16 (CA 125). Participants are assigned to the dual-target CAR-NK product that best matches their tumor antigen profile to reduce the risk of antigen escape.",[219,220,221,222],"Epithelial Ovarian Cancer","Primary Peritoneal Carcinoma","Fallopian Tube Carcinoma","Recurrent or Refractory Disease After Standard Therapies",[33,224,225,226,227,228,36,229],"Dual targeting","Mesothelin (MSLN)","Folate Receptor alpha","MUC16","Intraperitoneal administration","Ovarian cancer","2026-05-25",{"date":232,"type":48},"2026-06-01",{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":237,"slug":238,"hasResults":12,"nctId":239,"briefTitle":240,"officialTitle":241,"acronym":242,"eligibilityCriteria":243,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":244,"targetDuration":4,"studyType":24,"phases":245,"briefSummary":246,"conditions":247,"keywords":250,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":230,"lastUpdatePostDateStruct":253,"startDateStruct":254,"completionDateStruct":255,"leadSponsor":257,"locationsCount":56},"100637258","phase-1-egfrher2-dual-target-car-nk-cells-for-recurrent-or-metastatic-hnscc-100637258","NCT07617805","EGFR\u002FHER2 Dual-Target CAR-NK Cells for Recurrent or Metastatic HNSCC","A Phase 1\u002F2, Open-Label, Biomarker-Enriched Study of Allogeneic EGFR\u002FHER2 Dual-Target CAR-NK Cells Following Fludarabine\u002FCyclophosphamide Lymphodepletion in Adults With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma","DUAL-HN","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that is recurrent or metastatic and not amenable to curative surgery or radiotherapy.\n* Tumor meets protocol-defined central biomarker criteria for both EGFR and HER2 \u002F ERBB2. Suggested example thresholds: EGFR membranous IHC 2+ \u002F 3+ in at least 50% of viable tumor cells and HER2 IHC 2+ \u002F 3+ in at least 10% of viable tumor cells and \u002F or protocol-defined genomic amplification \u002F activating alteration.\n* Disease progression on or after at least one prior systemic regimen for recurrent \u002F metastatic disease, including platinum therapy and PD-1 \u002F PD-L1 inhibitor unless contraindicated or not appropriate. Prior cetuximab is allowed.\n* At least one measurable lesion by RECIST 1.1.\n* ECOG performance status 0 to 1.\n* Adequate marrow, renal, hepatic, cardiac, and pulmonary function per protocol-defined laboratory thresholds.\n* Life expectancy of at least 12 weeks.\n* Availability of archival tissue or willingness to provide fresh tumor tissue for central biomarker testing; willingness to undergo serial blood sampling and optional research biopsy if medically feasible.\n* Negative pregnancy test for participants of childbearing potential and agreement to use highly effective contraception during protocol-defined treatment and follow-up windows.\n* Ability to understand and sign informed consent.\n\nExclusion Criteria:\n\n* Nasopharyngeal carcinoma, salivary gland malignancy, cutaneous squamous cell carcinoma, non-squamous histology, or carcinoma of unknown primary.\n* Untreated, unstable, or symptomatic central nervous system metastases or leptomeningeal disease.\n* Prior gene-modified adoptive cell therapy (for example CAR-T, CAR-NK, or TCR-T) within a protocol-defined washout period, or prior allogeneic stem-cell transplant with active graft-versus-host disease.\n* Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active hepatitis B or C with detectable viral load; or uncontrolled HIV infection.\n* Active autoimmune disease requiring systemic immunosuppression, or chronic corticosteroid use above the protocoldefined threshold before lymphodepletion.\n* Clinically significant interstitial lung disease, oxygen dependence, or another serious pulmonary condition that would materially increase cell-therapy risk.\n* Clinically significant cardiovascular disease including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, uncontrolled hypertension, or symptomatic heart failure.\n* Major surgery within 28 days before lymphodepletion, or anticancer therapy \u002F investigational therapy within the protocol-defined washout window.\n* Pregnancy or breastfeeding.\n* Known severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients.\n* Any medical, psychiatric, or social condition that, in the investigator's judgment, would compromise safety, protocol compliance, or informed consent.",{"count":188,"type":23},[26,27],"This example Phase 1\u002F2 protocol evaluates allogeneic EGFR\u002FHER2 dual-target CAR-NK cells in adults with recurrent or metastatic HNSCC whose tumors meet protocol-defined co-expression criteria for EGFR and HER2\u002FERBB2. The study is designed as a biomarker-enriched, open-label, non-randomized trial with a dose-escalation safety lead-in followed by an expansion cohort at the recommended Phase 2 dose (RP2D).",[248,249],"Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma","Biomarker-positive EGFR\u002FHER2- Expressing HNSCC",[37,251,33,36,165,252,41,42,77],"Head and neck squamous cell carcinoma (HNSCC)","Biomarker-enriched",{"date":232,"type":48},{"date":50,"type":48},{"date":256,"type":23},"2028-05-17",{"name":54,"class":55},{"id":259,"slug":260,"hasResults":12,"nctId":261,"briefTitle":262,"officialTitle":263,"acronym":264,"eligibilityCriteria":265,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":266,"targetDuration":4,"studyType":24,"phases":267,"briefSummary":268,"conditions":269,"keywords":272,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":277,"lastUpdatePostDateStruct":278,"startDateStruct":280,"completionDateStruct":281,"leadSponsor":283,"locationsCount":56},"100639274","phase-1-target-selected-car-nk-cells-cd30-cd5-or-mesothelin-for-relapsedrefractory-b2-thymoma-or-thymic-carcinoma-100639274","NCT07598955","Target-Selected CAR-NK Cells (CD30, CD5, or Mesothelin) for Relapsed\u002FRefractory B2 Thymoma or Thymic Carcinoma","A Phase 1\u002F2, Open-Label, Target-Selected Study of Allogeneic CAR-NK Cells Directed to CD30, CD5, or Mesothelin in Patients With Relapsed\u002FRefractory B2 Thymoma or Thymic Carcinoma","SELECT-NK-THYM","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically confirmed B2 thymoma or thymic carcinoma that is unresectable, metastatic, or recurrent.\n* Relapsed or refractory after at least 1 prior systemic therapy (including a platinum-based regimen for thymic carcinoma when appropriate) or no standard curative option available.\n* Tumor antigen positivity for at least one of the following by central laboratory assessment: CD30, CD5, or mesothelin. Cohort assignment is based on the dominant target (pre-specified algorithm) and feasibility of manufacturing\u002Favailability.\n* Measurable disease per RECIST v1.1 (or evaluable disease if measurable disease is not feasible; to be specified).\n* ECOG performance status 0-1 (0-2 may be permitted in expansion at investigator discretion).\n* Adequate organ function: ANC ≥ 1.0 x 10\\^9\u002FL, platelets ≥ 75 x 10\\^9\u002FL, hemoglobin ≥ 8 g\u002FdL (transfusions allowed), AST\u002FALT ≤ 3 x ULN (≤ 5 x ULN with liver involvement), total bilirubin ≤ 1.5 x ULN (except Gilbert's), creatinine clearance ≥ 50 mL\u002Fmin.\n* Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception.\n* Ability to understand and sign informed consent.\n\nExclusion Criteria:\n\n* Active central nervous system involvement by malignancy requiring immediate therapy.\n* Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 90 days or unresolved ≥Grade 2 toxicity from prior cellular therapy.\n* Uncontrolled infection, including active tuberculosis, or uncontrolled hepatitis B or C infection; known uncontrolled HIV infection.\n* Clinically significant autoimmune disease requiring systemic immunosuppression (e.g., \\>10 mg\u002Fday prednisone equivalent) within 14 days of conditioning, except for stable endocrine replacement.\n* Prior allogeneic hematopoietic stem cell transplant with active graft-versus-host disease or ongoing immunosuppression.\n* Significant cardiovascular disease (e.g., NYHA class III\u002FIV heart failure, recent myocardial infarction), uncontrolled arrhythmia, or QTc prolongation felt to increase risk.\n* Pregnancy or breastfeeding.\n* Concurrent participation in another interventional trial with an investigational anticancer agent within 21 days (washout required).\n* Any condition that, in the investigator's judgment, would interfere with safe participation or interpretation of results.",{"count":100,"type":23},[26,27],"This Phase 1\u002F2 study evaluates the safety, tolerability, and preliminary efficacy of target-selected CAR-natural killer (CAR-NK) cells in adults with relapsed or refractory B2 thymoma or thymic carcinoma. Participants undergo centralized tumor antigen assessment (CD30, CD5, and mesothelin). Based on the dominant and clinically actionable antigen expression profile, each participant is assigned to one of three parallel cohorts (CD30-CAR-NK, CD5-CAR-NK, or mesothelin-CAR-NK). All cohorts use the same lymphodepleting conditioning regimen followed by CAR-NK infusion(s).",[270,271],"B2 Thymoma","Thymic Carcinoma",[33,198,36,273,274,275,40,39,276],"Thymic epithelial tumor","CD30","CD5","Solid tumor immunotherapy","2026-05-14",{"date":279,"type":48},"2026-05-20",{"date":50,"type":48},{"date":282,"type":23},"2028-04-17",{"name":54,"class":55},{"id":285,"slug":286,"hasResults":12,"nctId":287,"briefTitle":288,"officialTitle":289,"acronym":290,"eligibilityCriteria":291,"healthyVolunteers":12,"sex":214,"minAge":19,"maxAge":20,"enrollmentInfo":292,"targetDuration":4,"studyType":24,"phases":293,"briefSummary":294,"conditions":295,"keywords":297,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":299,"startDateStruct":301,"completionDateStruct":302,"leadSponsor":303,"locationsCount":56},"100638813","phase-1-dual-target-car-nk-cells-in-recurrent-or-refractory-epithelial-ovarian-cancer-100638813","NCT07589543","Dual-Target CAR-NK Cells in Recurrent or Refractory Epithelial Ovarian Cancer","A Phase 1\u002F2, Open-Label, Dose-Escalation and Expansion Study of Dual-Target CAR-NK Cells (EB-DUALNK) Following Lymphodepleting Chemotherapy in Adults With Recurrent or Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma","EB-DUALNK-OV","Inclusion Criteria:\n\n* Age 18-75 years; able to provide written informed consent.\n* Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma that is recurrent or refractory after standard therapy (at least 2 prior systemic regimens), with measurable disease per RECIST v1.1 and ECOG performance status 0-1.\n* Tumor tissue available for antigen assessment. Participant must meet protocol-defined positivity for the selected dual-target pair (example: 1 target expressed in \\>=50% of tumor cells by IHC and the second target in \\>=20%).\n* Adequate organ function per protocol-specified labs; negative pregnancy test nd agrees to use effective contraception for a protocol-defined period after infusion.\n\nExclusion Criteria:\n\n* Active CNS metastases or carcinomatous meningitis (unless treated and stable for a protocol-defined period).\n* Prior gene-modified cell therapy targeting any of the study antigens (GD2, MUC1, PSMA, mesothelin) within 6 months.\n* Uncontrolled active infection (including uncontrolled HIV, HBV, or HCV) or active systemic fungal infection.\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina, uncontrolled arrhythmia) or LVEF \\\u003C50% .\n* Active autoimmune disease requiring systemic immunosuppression within 14 days prior to lymphodepletion (physiologic steroid replacement permitted).\n* History of organ transplantation or allogeneic hematopoietic stem cell transplantation.\n* Pregnant or breastfeeding.\n* Any condition that, in the investigator's judgment, would compromise participant safety or compliance.",{"count":188,"type":23},[26,27],"This study evaluates the safety, tolerability, and preliminary anti-tumor activity of EB-DUALNK, a dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy, in adults with recurrent or refractory epithelial ovarian cancer. Candidates for targeting include GD2, MUC1, PSMA, and mesothelin. After baseline biomarker assessment (tumor antigen expression), the program will select the most suitable dual-target pair for clinical testing. Participants will receive lymphodepleting chemotherapy followed by EB-DUALNK infusion and safety\u002Fresponse follow-up.",[219,296],"Epithelial Ovarian Cancer, Fallopian Tube or Peritoneum",[37,229,38,36,33,34,140,200,110,40],"2026-05-10",{"date":300,"type":48},"2026-05-15",{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":305,"slug":306,"hasResults":12,"nctId":307,"briefTitle":308,"officialTitle":309,"acronym":310,"eligibilityCriteria":311,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":312,"targetDuration":4,"studyType":24,"phases":313,"briefSummary":314,"conditions":315,"keywords":319,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":323,"startDateStruct":324,"completionDateStruct":325,"leadSponsor":326,"locationsCount":56},"100638267","phase-1-phase-12-study-of-eb-nk-301-allogeneic-trop2-car-nk-cells-in-advanced-trop2-expressing-solid-tumors-100638267","NCT07589530","Phase 1\u002F2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors","A Phase 1\u002F2, Open-Label, Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of EB-NK-301 (Allogeneic TROP2-Targeted CAR NK Cells) Following Lymphodepleting Chemotherapy in Adults With Advanced or Metastatic TROP2-Expressing Solid Tumors","SOLID-NK","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of informed consent.\n* Histologically or cytologically confirmed advanced or metastatic solid tumor with documented TROP2 expression (per local testing or central confirmation).\n* Disease progression on, intolerance to, or ineligibility for available standard therapy.\n* At least one measurable lesion per RECIST 1.1.\n* ECOG performance status 0 to 1.\n* Adequate organ function (hematologic, renal, hepatic) within protocol-defined limits.\n* Life expectancy ≥ 12 weeks.\n* Willingness to use effective contraception during study participation and for a protocol-defined period after last infusion (if of childbearing potential).\n* Ability to understand and willingness to sign written informed consent.\n\nExclusion Criteria:\n\n* Active central nervous system (CNS) metastases or leptomeningeal disease (unless treated and clinically stable for ≥ 4 weeks).\n* Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.\n* Uncontrolled active infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.\n* Active autoimmune disease requiring systemic immunosuppression.\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke within 6 months, uncontrolled arrhythmia).\n* Receipt of another investigational agent within 2 weeks (or 5 half-lives, whichever is longer) prior to lymphodepleting chemotherapy.\n* Prior gene-modified cellular therapy within 3 months prior to enrollment.\n* Systemic corticosteroid therapy \\> 10 mg\u002Fday prednisone equivalent within 7 days prior to lymphodepletion (excluding physiologic replacement).\n* Pregnant or breastfeeding.",{"count":22,"type":23},[26,27],"study evaluates EB-NK-301, an investigational off-the-shelf allogeneic CAR-NK cell product targeting TROP2, in adults with advanced or metastatic solid tumors that express TROP2 and have progressed after standard therapy.\n\nThe primary goals are to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine a recommended Phase 2 dose (RP2D). Secondary goals include preliminary anti-tumor activity, persistence of infused CAR-NK cells, and exploratory immune biomarkers.",[316,317,318],"Advanced Solid Tumors","Metastatic Solid Tumors","TROP2-Expressing Solid Tumors",[320,38,36,198,321,33,43,172,322],"Solid tumors","NK cell therapy","TROP2",{"date":300,"type":48},{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":328,"slug":329,"hasResults":12,"nctId":330,"briefTitle":331,"officialTitle":332,"acronym":333,"eligibilityCriteria":334,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":335,"targetDuration":4,"studyType":24,"phases":337,"briefSummary":338,"conditions":339,"keywords":343,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":347,"startDateStruct":348,"completionDateStruct":350,"leadSponsor":351,"locationsCount":56},"100637706","phase-1-dual-targeting-car-nk-cells-in-biomarker-selected-advanced-colorectal-cancer-100637706","NCT07589517","Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer","A Phase 1\u002F2, Biomarker-Assigned, Open-Label Dose Escalation and Expansion Study of Allogeneic Dual-Target CAR-NK Cells Targeting CEA (CEACAM5) and\u002For GUCY2C (GCC) With an Exploratory HER2\u002FERBB2-Positive Cohort in Subjects With Advanced or Metastatic Colorectal Cancer","DUO-CRC-NK-111","Inclusion Criteria:\n\n* Histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic and has progressed after, is intolerant to, or is ineligible for standard therapies.\n* Measurable disease per RECIST v1.1 (unless in minimal residual disease (MRD) or post-resection cohorts if a future amendment is planned).\n* Tumor antigen co-expression meeting central lab thresholds for one of the following pairs: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2.\n* ECOG performance status 0-1.\n* Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in protocol.\n* Recovered to Grade ≤1 from prior therapy-related toxicities (except stable Grade 2 neuropathy or alopecia).\n* Life expectancy ≥ 12 weeks.\n* Willingness to use effective contraception during study and for a protocol-defined period after cell infusion.\n\nExclusion Criteria:\n\n* Active, uncontrolled infection (including uncontrolled HBV\u002FHCV) or known uncontrolled HIV infection.\n* Active CNS metastases that are symptomatic or require escalating steroids. (Stable treated CNS disease may be allowed per protocol.)\n* Prior gene-modified cellular therapy (CAR-T\u002FCAR-NK\u002FTCR-T) within 6 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.\n* Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.\n* Concurrent anti-cancer therapy (other than protocol-permitted bridging) during the DLT window.\n* Pregnant or breastfeeding.\n* Significant cardiovascular disease (e.g., recent MI, uncontrolled arrhythmia), uncontrolled pulmonary disease, or other severe comorbidity that would increase risk.\n* Known hypersensitivity to study chemotherapy components (fludarabine\u002Fcyclophosphamide) or required supportive medications.\n* Any condition that, in the investigator's opinion, would interfere with study participation, safety monitoring, or interpretation of results.",{"count":336,"type":23},48,[26,27],"This Phase 1\u002F2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of an allogeneic dual-target chimeric antigen receptor natural killer (CAR-NK) cell product in adults with advanced or metastatic colorectal cancer (CRC). Participants are assigned to one of three dual-target arms based on tumor antigen co-expression: (1) CEA+GUCY2C, (2) CEA+HER2, or (3) GUCY2C+HER2. Following dose escalation, the most suitable target pair (based on safety, feasibility, and early efficacy\u002Fbiomarker signals) will be selected for dose expansion.",[340,341,342],"Colorectal Cancer","Metastatic Colorectal Adenocarcinoma","Unresectable Colorectal Cancer",[33,344,79,78,345,346,42,77,276,165,36],"Dual-target CAR","GUCY2C","GCC",{"date":300,"type":48},{"date":349,"type":48},"2026-02-02",{"date":177,"type":23},{"name":54,"class":55},{"id":353,"slug":354,"hasResults":12,"nctId":355,"briefTitle":356,"officialTitle":357,"acronym":358,"eligibilityCriteria":359,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":360,"targetDuration":4,"studyType":24,"phases":361,"briefSummary":362,"conditions":363,"keywords":366,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":371,"lastUpdatePostDateStruct":372,"startDateStruct":374,"completionDateStruct":375,"leadSponsor":376,"locationsCount":56},"100635336","phase-1-dual-target-cldn182her2-car-nk-cells-for-advanced-gastricgej-cancer-100635336","NCT07551362","Dual-target CLDN18.2\u002FHER2 CAR-NK Cells for Advanced Gastric\u002FGEJ Cancer","A Phase 1\u002F2, Open-label, Multicenter Study of Allogeneic Dual-target CLDN18.2\u002FHER2 (ERBB2) CAR-NK Cells After Fludarabine\u002FCyclophosphamide Lymphodepletion in","DUET-GEJ","Inclusion Criteria:\n\n* Signed informed consent before any study-specific procedure.\n* Age 18 to 75 years.\n* Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.\n* Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+\u002FISH+ using gastric\u002FGEJ testing criteria.\n* Disease progression after at least 2 prior systemic regimens for advanced disease, including a fluoropyrimidine and platinum agent unless contraindicated or not tolerated. If HER2-positive, prior HER2-directed therapy is expected unless unavailable, contraindicated, or not tolerated.\n* At least 1 measurable lesion according to RECIST v1.1.\n* ECOG performance status 0 or 1.\n* Life expectancy of at least 12 weeks.\n* Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.\n* Recovery of prior treatment-related toxicities to Grade 1 or baseline, except alopecia or stable endocrine replacement therapy.\n* Willingness to provide archival tumor tissue or fresh biopsy material if archival tissue is inadequate for central biomarker confirmation.\n* Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during the protocol-defined period\n\nExclusion Criteria:\n\n* Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).\n* Active or untreated central nervous system metastases or leptomeningeal disease.\n* Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.\n* Active autoimmune disease requiring systemic immunosuppression.\n* Clinically significant uncontrolled cardiovascular disease, including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or severe heart failure.\n* Active gastrointestinal perforation, uncontrolled upper GI bleeding, clinically significant bowel obstruction, or unstable gastric ulcer.\n* History of solid-organ transplantation or prior allogeneic hematopoietic stem-cell transplantation with active graft-versus-host disease.\n* Requirement for systemic corticosteroids above physiologic replacement (for example, \\>10 mg\u002Fday prednisone equivalent) within 7 days before lymphodepletion.\n* Pregnancy or breastfeeding.\n* Another active malignancy requiring systemic therapy, except for adequately treated non-melanoma skin cancer, carcinoma in situ, or other protocol-allowed low-risk malignancies.\n* Any medical, psychiatric, or social condition that, in the investigator's judgment, would make study participation unsafe or would interfere with interpretation of study results.",{"count":100,"type":23},[26,27],"This example planning study proposes a phase 1\u002F2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. CLDN18.2 is selected as the anchor antigen because it has the more disease-specific gastric\u002FGEJ cell-therapy development footprint, while HER2 is retained as the complementary second antigen to address co-expressing or heterogeneous disease. Phase 1 uses a 3+3 dose-escalation design after fludarabine\u002Fcyclophosphamide lymphodepletion followed by three intravenous CAR-NK infusions on Days 0, 3, and 7. Phase 2 expansion evaluates the recommended phase 2 dose and preliminary antitumor activity",[364,365],"Advanced Gastric Adenocarcinoma","Advanced Gastroesophageal Junction Adenocarcinoma",[276,367,368,369,33,370,167,42,77],"Gastric cancer","GEJ cancer","Adoptive cellular immunotherapy","Allogeneic NK cell therapy","2026-04-18",{"date":373,"type":48},"2026-04-24",{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":378,"slug":379,"hasResults":12,"nctId":380,"briefTitle":381,"officialTitle":382,"acronym":4,"eligibilityCriteria":383,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":384,"targetDuration":4,"studyType":24,"phases":385,"briefSummary":386,"conditions":387,"keywords":393,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":371,"lastUpdatePostDateStruct":400,"startDateStruct":401,"completionDateStruct":402,"leadSponsor":403,"locationsCount":56},"100635334","phase-1-dual-targeting-car-nk-cells-for-recurrentprogressive-glioblastoma-and-high-grade-glioma-100635334","NCT07551336","Dual-Targeting CAR-NK Cells for Recurrent\u002FProgressive Glioblastoma and High-Grade Glioma","A Phase 1, First-in-Human, Biomarker-Guided, Dose-Escalation and Expansion Study of Locoregional Dual-Targeting CAR-NK Cells Directed Against IL13Rα2, EGFR\u002FEGFRvIII, and\u002For B7-H3 (CD276) in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy.\n* Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement.\n* Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and\u002For EGFRvIII, B7-H3 (CD276).\n* Karnofsky Performance Status (KPS) ≥ 60.\n* Adequate organ function (hematologic, renal, hepatic) as defined by protocol laboratory criteria.\n* Ability to undergo brain MRI with contrast (unless contraindicated and alternative imaging is permitted).\n* Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.\n* Ability to understand and willingness to sign informed consent.\n\nExclusion Criteria:\n\n* Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection).\n* Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol).\n* Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.\n* Requirement for high-dose systemic corticosteroids (e.g., \\>4 mg\u002Fday dexamethasone equivalent) within 7 days prior to lymphodepletion\u002Finfusion (physiologic replacement permitted).\n* Prior gene-modified cellular therapy (e.g., prior CAR-T\u002FCAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR\u002FEGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments.\n* Diffuse leptomeningeal disease as the only site of disease, or anatomy that precludes safe catheter placement (unless specifically allowed by protocol).\n* Uncontrolled seizures despite optimal medical therapy.\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk with lymphodepletion or infusion procedures.\n* Pregnant or breastfeeding.\n* Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence.",{"count":100,"type":23},[26],"This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR\u002FEGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.",[388,389,390,391,392],"Malignant Glioma","High-Grade Gliomas","Glioblastoma","Recurrent High-Grade Gliomas","Recurrent Glioblastoma",[33,224,39,394,41,395,396,397,398,399],"IL13Rα2","EGFRvIII","B7-H3 (CD276)","Locoregional","Intracavitary","Ommaya reservoir",{"date":373,"type":48},{"date":50,"type":48},{"date":282,"type":23},{"name":54,"class":55},{"id":405,"slug":406,"hasResults":12,"nctId":407,"briefTitle":408,"officialTitle":409,"acronym":410,"eligibilityCriteria":411,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":412,"targetDuration":4,"studyType":24,"phases":413,"briefSummary":414,"conditions":415,"keywords":417,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":371,"lastUpdatePostDateStruct":421,"startDateStruct":422,"completionDateStruct":423,"leadSponsor":424,"locationsCount":56},"100635335","phase-1-dual-target-cd70caix-car-nk-cells-for-advanced-clear-cell-renal-cell-carcinoma-100635335","NCT07551349","Dual-target CD70\u002FCAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma","An Open-Label, Multicenter, Phase 1\u002F2 Study of Allogeneic Dual-target CD70\u002FCAIX (CA9) Chimeric Antigen Receptor Natural Killer Cells in Adults With Advanced or Metastatic Clear Cell Renal Cell Carcinoma","DUAL-NK RCC","Inclusion Criteria:\n\n* Written informed consent and willingness to comply with protocol procedures.\n* Age \\>= 18 years at the time of consent.\n* Histologically confirmed unresectable or metastatic clear cell RCC, or RCC with a clear-cell component, with radiographic progression after standard therapy.\n* Prior exposure to at least one PD-1 \u002F PD-L1-based regimen and at least one VEGF-pathway targeted regimen, or documented intolerance \u002F unsuitability for available standard systemic options.\n* At least one measurable lesion by RECIST 1.1.\n* Available archival tumor tissue or willingness to undergo fresh biopsy for central biomarker testing; protocoldefined tumor positivity for CD70 and\u002For CAIX is required. Dual-positive cases are preferred for the biomarkerexpansion portion.\n* ECOG performance status 0-1.\n* Adequate marrow, liver, cardiac, pulmonary, and renal function as defined by the protocol (for example, ANC, platelets, bilirubin, AST\u002FALT, creatinine clearance, oxygen saturation, and left ventricular function within protocoldefined limits).\n* Life expectancy of at least 12 weeks.\n* Negative pregnancy test for participants of childbearing potential and agreement to highly effective contraception during protocol-defined risk windows.\n* Previously treated brain metastases are allowed if clinically stable and off escalating corticosteroids for at least 14 days before lymphodepletion.\n\nExclusion Criteria:\n\n* Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.\n* Prior gene-modified cellular therapy (including prior CAR-T, CAR-NK, CAR-NKT, or TCR-engineered therapy) within the protocol-defined washout window.\n* Prior allogeneic stem cell transplant or solid organ transplant with ongoing clinically significant immunosuppression.\n* Active autoimmune disease requiring systemic immunosuppressive treatment; physiologic replacement doses are permitted.\n* Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, tuberculosis, or sepsis.\n* Clinically significant hepatobiliary disease that could increase risk from CAIX-directed therapy, such as active cholangitis, primary sclerosing cholangitis, biliary obstruction, Child-Pugh B\u002FC cirrhosis, or prior hepatic venoocclusive disease.\n* Clinically significant cardiovascular disease (for example, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful heart failure).\n* Systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days before lymphodepletion, unless required as physiologic replacement.\n* Pregnancy or breastfeeding.\n* Another active invasive malignancy requiring systemic treatment, except for protocol-defined low-risk exceptions.\n* Known hypersensitivity to fludarabine, cyclophosphamide, or a critical study-product excipient.",{"count":100,"type":23},[26,27],"Phase 1\u002F2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70\u002FCAIX CAR-NK cells after fludarabine\u002Fcyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. The study is designed to determine a recommended dose and schedule, characterize hepatobiliary safety, and explore whether CD70-high, CAIX-high, or dual-high tumors derive the greatest benefit. Biomarker-defined activity signals will be used to guide whether later development should prioritize CD70, CAIX\u002FCA9, or continued dual-targeting.",[416],"Advanced or Metastatic Clear Cell Renal Cell Carcinoma",[418,419,420],"RCC","kidney cancer","clear cell renal cell carcinoma",{"date":373,"type":48},{"date":349,"type":48},{"date":282,"type":23},{"name":54,"class":55},{"id":426,"slug":427,"hasResults":12,"nctId":428,"briefTitle":429,"officialTitle":430,"acronym":431,"eligibilityCriteria":432,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":433,"targetDuration":4,"studyType":24,"phases":435,"briefSummary":436,"conditions":437,"keywords":445,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":462,"lastUpdatePostDateStruct":463,"startDateStruct":465,"completionDateStruct":466,"leadSponsor":468,"locationsCount":56},"100633197","phase-1-adaptive-dual-target-car-t-cells-for-relapsed-or-refractory-hematologic-malignancies-100633197","NCT07523555","Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies","A Phase 1\u002F2, Open-Label, Nonrandomized, Multi-arm Umbrella Study of Biomarker-Selected Dual-Target CAR-T Cell Modules in Adults With Relapsed or Refractory Hematologic Malignancies","ADAPT-HEM","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Pathologically or cytologically confirmed eligible disease: B-ALL; B-cell NHL\u002FCLL\u002FSLL; multiple myeloma\u002Fplasma cell leukemia; AML\u002Fhigh-risk MDS\u002FBPDCN; or T-ALL\u002FT-LBL\u002Fperipheral T-cell lymphoma.\n* Relapsed or refractory disease after at least 2 prior lines of therapy, or no curative\u002Fapproved standard option judged appropriate by the investigator.\n* Central laboratory confirmation that at least one active dual-target module is suitable based on malignant-cell antigen co-expression and safety review.\n* Measurable or otherwise evaluable disease by disease-specific response criteria.\n* ECOG performance status 0 to 2.\n* Adequate organ function: LVEF \\>= 45%; creatinine clearance \\>= 40 mL\u002Fmin; AST\u002FALT \\\u003C= 3 x ULN; total bilirubin \\\u003C= 1.5 x ULN unless due to Gilbert syndrome; oxygen saturation \\>= 92% on room air.\n* Adequate hematologic reserve unless cytopenia is clearly disease-related.\n* Ability to undergo leukapheresis and willingness to comply with study procedures and follow-up.\n* If prior allogeneic HSCT: at least 100 days from transplant, no uncontrolled GVHD, and no systemic immunosuppression above physiologic steroid replacement.\n* Negative pregnancy test for participants of childbearing potential and agreement to use effective contraception during protocol-defined risk periods.\n* Written informed consent obtained before any study-specific procedure.\n\nExclusion Criteria:\n\n* \\- Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection, or clinical sepsis.\n* Active symptomatic CNS involvement requiring escalating therapy; previously treated\u002Fstable CNS disease may be allowed if defined prospectively in the final protocol.\n* Prior gene-modified cellular therapy within 12 weeks before leukapheresis, or unresolved \\>= Grade 3 toxicity from prior anticancer therapy\n* Need for urgent cytoreduction such that manufacturing delay would create unacceptable clinical risk.\n* Active autoimmune disease requiring systemic immunosuppression, except limited replacement-dose steroids or protocol-permitted topical\u002Finhaled therapy.\n* Prior solid organ transplant.\n* Clinically significant cardiovascular disease, uncontrolled arrhythmia, decompensated heart failure, myocardial infarction within 6 months, or recent stroke within 6 months.\n* Uncontrolled HIV, HBV, or HCV viremia.\n* Pregnancy or breastfeeding.\n* Another active malignancy requiring systemic therapy, unless low-risk and definitively treated per protocol-defined exceptions.\n* Known hypersensitivity to fludarabine, cyclophosphamide, or critical product excipients.\n* Inability to manufacture a releaseable CAR-T product or failure to meet module-specific product-release criteria.\n* Any medical, psychiatric, or social condition that, in the investigator's judgment, would increase risk, impair compliance, or confound interpretation of study results.",{"count":434,"type":23},96,[26,27],"Phase 1\u002F2 umbrella study evaluates biomarker-selected dual-target CAR-T cell modules for adults with relapsed or refractory hematologic malignancies. After central antigen co-expression screening, participants are assigned to the most appropriate active dual-target module: CD19\u002FCD22, CD19\u002FCD20, BCMA\u002FCD19, BCMA\u002FCD38, BCMA\u002FGPRC5D, CD33\u002FCD123, CD33\u002FCLL1, or CD5\u002FCD7. Phase 1 determines safety, dose-limiting toxicities, and the recommended phase 2 dose for each module; phase 2 estimates preliminary antitumor activity, including overall response rate and MRD-negative response.\n\nLymphodepletion with fludarabine\u002Fcyclophosphamide precedes infusion. The design is intended to reduce antigen escape by matching disease biology and target co-expression to a rational dual-target strategy.",[438,439,440,441,442,443,444],"Relapsed\u002FRefractory B-cell Acute Lymphoblastic Leukemia","Relapsed\u002FRefractory B-cell Non-Hodgkin Lymphoma or CLL\u002FSLL","Relapsed\u002FRefractory Multiple Myeloma or Plasma Cell Leukemia","Relapsed\u002FRefractory Acute Myeloid Leukemia, High-risk Myelodysplastic Neoplasm","BPDCN; Relapsed\u002FRefractory T-cell Acute Lymphoblastic Leukemia","T-lymphoblastic Lymphoma","Peripheral T-cell Lymphoma",[446,447,448,449,450,451,452,453,275,454,455,456,457,458,459,460,461],"BCMA","biomarker-selected","CD19","CD20","CD22","CD33","CD38","CD123","CD7","CLL1\u002FCLEC12A","dual-target CAR-T","GPRC5D","hematologic malignancy","MRD negativity","antigen escape","umbrella trial","2026-04-05",{"date":464,"type":48},"2026-04-13",{"date":50,"type":48},{"date":467,"type":23},"2028-02-17",{"name":54,"class":55},{"id":470,"slug":471,"hasResults":12,"nctId":472,"briefTitle":473,"officialTitle":474,"acronym":475,"eligibilityCriteria":476,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":477,"enrollmentInfo":478,"targetDuration":4,"studyType":24,"phases":480,"briefSummary":481,"conditions":482,"keywords":485,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":462,"lastUpdatePostDateStruct":494,"startDateStruct":495,"completionDateStruct":496,"leadSponsor":497,"locationsCount":56},"100633196","phase-1-select-sle-biomarker-guided-car-t-target-selection-for-refractory-lupus-100633196","NCT07523542","SELECT-SLE: Biomarker-Guided CAR-T Target Selection for Refractory Lupus","A Phase 1\u002F2, Open-Label, Biomarker-Guided, Non-Randomized, Multicenter Study of Autologous CAR-T Cell Therapy Targeting CD19 or BCMA in Adults With Refractory Systemic Lupus Erythematosus With or Without Active Lupus Nephritis.","SELECT-SLE","Inclusion Criteria:\n\n* 1\\. Age 18 to 70 years at consent. 2. Meets 2019 EULAR\u002FACR classification criteria for SLE, with total score \\>= 10.\n\n  3\\. Active refractory disease at screening, defined by SELENA-SLEDAI \\>= 8, or at least one BILAG A domain, or at least two BILAG B domains, or active lupus nephritis with significant proteinuria and active urinary sediment.\n\n  4\\. Inadequate response, intolerance, or contraindication to at least 2 prior standard systemic regimens, including at least 1 immunosuppressant or biologic used for SLE or lupus nephritis. 5. Demonstrable targetable biology and assignment to one protocol arm: CD19 arm for measurable CD19-positive B-cell \u002F B-cell-dominant disease, or BCMA arm for BCMA-positive plasmablast \u002F plasma-cell-dominant disease and\u002For persistent serologic activity after prior B-cell depletion. 6. If active lupus nephritis is present, biopsy-proven class III, IV, V, or mixed proliferative \u002F membranous LN within the previous 24 months, or investigator confirmation that repeat biopsy is unsafe but the clinical picture strongly supports active LN. 7. Adequate organ function: hemoglobin \\>= 8.5 g\u002FdL, ANC \\>= 1.0 x 10\\^9\u002FL, platelets \\>= 50 x 10\\^9\u002FL, AST \u002F ALT \\\u003C= 2.5 x ULN, creatinine clearance \\>= 30 mL\u002Fmin, bilirubin \\\u003C= 2.0 mg\u002FdL unless otherwise explained, and LVEF \\>= 50%.\n\n  8\\. Adequate venous access and eligibility for leukapheresis. 9. Negative pregnancy test and agreement to use effective contraception for 12 months after infusion.\n\n  10\\. Ability to discontinue prohibited SLE medications per washout rules and willingness to comply with inpatient observation and long-term follow-up. 11. Written informed consent.\n\nExclusion Criteria:\n\n* 1\\. Active uncontrolled infection, including active tuberculosis, hepatitis B or C with active replication, or HIV.\n\n  2\\. Prior CAR-T therapy or prior CD19- or BCMA-directed cell therapy. 3. Severe active CNS lupus requiring urgent escalation of immunosuppression, uncontrolled seizure disorder, or stroke within 60 days before screening. 4. End-stage organ failure not expected to improve with immune reset, such as dialysis-dependent kidney failure, uncontrolled advanced heart failure, or ICU-level respiratory instability. 5. Active malignancy or history of malignancy within 5 years, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or other low-risk malignancy in durable remission. 6. Pregnant or breastfeeding. 7. Allogeneic hematopoietic stem cell transplant or solid organ transplant history.\n\n  8\\. Contraindication to fludarabine, cyclophosphamide, leukapheresis, or standard rescue medications for CRS \u002F ICANS. 9. Live vaccine within 4 weeks before lymphodepletion. 10. Participation in another interventional clinical study within 3 months before enrollment.\n\n  11\\. Uncontrolled psychiatric disease, active substance misuse, or social circumstances that would impair adherence.\n\n  12\\. Any condition that, in the investigator's judgment, makes participation unsafe or confounds interpretation of the study endpoints.","70 Years",{"count":479,"type":23},24,[26,27],"study evaluates a biomarker-guided strategy to assign adults with refractory SLE to autologous CAR-T therapy targeting either CD19 or BCMA. Participants undergo centralized screening immunophenotyping to determine whether their disease appears B-cell-dominant (CD19-preferred) or plasma-cell-dominant (BCMA-preferred), followed by leukapheresis, lymphodepletion, and a single CAR-T infusion. The main goals are to assess safety, determine a recommended Phase 2 dose within each arm, and estimate remission rates by Week 24.",[483,484],"REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS","Lupus Nephritis",[486,487,446,488,489,448,490,491,492,493],"autologous T cells","B-cell depletion","biomarker-guided therapy","CAR-T","immune reset","lupus nephritis","plasma-cell depletion","refractory lupus",{"date":464,"type":48},{"date":50,"type":48},{"date":88,"type":23},{"name":54,"class":55},{"id":499,"slug":500,"hasResults":12,"nctId":501,"briefTitle":502,"officialTitle":503,"acronym":504,"eligibilityCriteria":505,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":506,"targetDuration":4,"studyType":24,"phases":508,"briefSummary":509,"conditions":510,"keywords":513,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":462,"lastUpdatePostDateStruct":538,"startDateStruct":539,"completionDateStruct":540,"leadSponsor":541,"locationsCount":56},"100633195","phase-1-biomarker-guided-dual-target-car-t-cells-for-advanced-solid-tumors-100633195","NCT07523529","Biomarker-Guided Dual-Target CAR-T Cells for Advanced Solid Tumors","A Phase 1\u002F2, Open-Label, Biomarker-Guided Master Protocol Evaluating Autologous Dual-Target CAR-T Cells Selected From a Predefined Target Library in Adults With Advanced Solid Tumors","SELECT-2CAR","Inclusion Criteria:\n\n* Age 18-75 years at consent\n* Histologically or cytologically confirmed advanced unresectable, metastatic, or recurrent solid malignancy (including recurrent high-grade glioma for CNSspecific pairs) for which standard curative therapy does not exist, is not tolerated, or has failed.\n* At least one predefined dual-target pair qualifies on central biomarker review. Recommended working thresholds: primary antigen \\>= 2+ intensity in \\>= 50% of viable tumor cells (or pair-specific equivalent) AND secondary antigen detectable in \\>= 25% of viable tumor cells, with acceptable normal-tissue risk after pathology review\n* At least 1 measurable lesion by RECIST 1.1, or measurable \u002F evaluable disease by RANO for CNS cohorts.\n* ECOG performance status 0-1 (CNS cohort may allow Karnofsky \\>= 70 or ECOG 0-2 if justified).\n* Adequate organ function: ANC \\>= 1.0 x 10\\^9\u002FL, platelets \\>= 75 x 10\\^9\u002FL, hemoglobin \\>= 8 g\u002FdL, creatinine clearance \\>= 50 mL\u002Fmin, AST \u002F ALT \\\u003C= 3 x ULN (\\\u003C= 5 x ULN if liver involvement), total bilirubin \\\u003C= 1.5 x ULN unless Gilbert syndrome, LVEF \\>= 45%, oxygen saturation \\>= 92% on room air.\n* Recovered to Grade \\\u003C= 1 from acute toxicities of prior anticancer therapy (except alopecia, stable endocrinopathies, or other protocol-allowed residual toxicities).\n* Adequate venous access and ability to undergo leukapheresis; successful manufacture of a release-qualified autologous dual-target CAR-T product.\n* Life expectancy \\>= 12 weeks.\n* Negative pregnancy test for persons of childbearing potential and agreement to use highly effective contraception per protocol.\n* Ability to understand and sign informed consent and comply with study follow-up, including long-term gene-modified cell monitoring.\n\nExclusion Criteria:\n\n* No qualifying target pair after central review, or target pair considered unsafe because of unacceptable predicted ontarget \u002F off-tumor risk.\n* Prior gene-modified cellular therapy directed against the same target pair within 6 months, or persistent clinically significant toxicity from prior cell \u002F gene therapy.\n* Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active tuberculosis; uncontrolled HIV; active hepatitis B or C with detectable \u002F unsafe viral burden.\n* Need for systemic corticosteroids \\> 10 mg prednisone equivalent daily or other systemic immunosuppressive therapy within 7 days before lymphodepletion, unless specifically allowed for physiologic replacement or CNS edema management per cohort rules.\n* Active autoimmune disease requiring systemic immunosuppression within the past 2 years, except protocol-allowed stable conditions.\n* Clinically significant cardiovascular disease (for example uncontrolled arrhythmia, recent myocardial infarction, unstable angina, decompensated heart failure), severe pulmonary compromise, or other major comorbidity making cell therapy unsafe.\n* Active symptomatic CNS hemorrhage, uncontrolled seizures, or uncontrolled intracranial hypertension; leptomeningeal disease requiring urgent intervention unless explicitly allowed in a CNS-specific cohort.\n* Pregnancy or breastfeeding.\n* Concurrent second malignancy requiring active systemic treatment, except certain low-risk or definitively treated cancers allowed by protocol.\n* Any condition that, in the investigator's judgment, would interfere with safe participation, product manufacture, infusion, or interpretation of results.",{"count":507,"type":23},72,[26,27],"This is a multicenter, open-label, Phase 1\u002F2 master protocol evaluating autologous dual-target CAR-T cell therapy in adults with advanced solid cancers. After central biomarker screening, each participant is assigned the best-matched dual-target construct from a predefined target-pair library. The trial is designed to test whether biomarkerguided dual targeting can improve tumor control, reduce antigenescape risk, and preserve safety in solid tumors.",[511,512],"Advanced Unresectable","Metastatic",[514,515,516,517,518,519,520,521,167,456,41,395,140,522,523,524,42,525,526,40,200,527,528,529,530,531,532,110,533,534,535,536,537],"antigen co-expression","B7-H3","bi-specific CAR-T","biomarkerguided","CD133","CD44","CD56","CD70","gastric cancer","glioblastoma","GPC3","hepatocellular carcinoma","IL13Ralpha2","NKG2D","NSCLC","ovarian cancer","pancreatic cancer","PD-L1","prostate cancer","solid tumors","tandem CAR-T","TRAIL-R2","triple-negative breast cancer","VEGFR1",{"date":464,"type":48},{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":543,"slug":544,"hasResults":12,"nctId":545,"briefTitle":546,"officialTitle":547,"acronym":548,"eligibilityCriteria":549,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":550,"targetDuration":4,"studyType":24,"phases":551,"briefSummary":552,"conditions":553,"keywords":555,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":563,"lastUpdatePostDateStruct":564,"startDateStruct":566,"completionDateStruct":567,"leadSponsor":568,"locationsCount":56},"100632217","phase-1-dual-target-mslnfap-car-nk-cells-for-pleural-and-peritoneal-mesothelioma-100632217","NCT07510815","Dual-Target MSLN\u002FFAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma","A Phase 1\u002F2, Open-Label, Nonrandomized, Biomarker-Guided Study of Locoregional Allogeneic Dual-Target Mesothelin (MSLN) \u002F Fibroblast Activation Protein (FAP) Chimeric Antigen Receptor Natural Killer Cells in Adults With Unresectable, Recurrent, or Refractory Pleural or Peritoneal Mesothelioma","DUAL-MESO-NK","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically confirmed malignant pleural mesothelioma or malignant peritoneal mesothelioma; unresectable, recurrent, metastatic, or refractory disease.\n* Prior receipt of at least one standard systemic regimen for mesothelioma, or documented ineligibility, intolerance, or refusal of standard therapy considered reasonable by the investigator.\n* Central biomarker confirmation of MSLN-positive tumor cells and FAP-positive tumorassociated stroma at protocol-defined thresholds.\n* At least one measurable or evaluable lesion by cohort-appropriate imaging criteria.\n* ECOG performance status 0 to 1.\n* Adequate bone marrow, renal, hepatic, coagulation, cardiac, and pulmonary function to undergo lymphodepletion and locoregional cell infusion.\n* Safe procedural access for intrapleural or intraperitoneal administration, as applicable.\n* Recovery to Grade 1 or better from prior anticancer therapy toxicities, except alopecia, stable neuropathy, or controlled endocrine replacement.\n* Life expectancy of at least 12 weeks.\n* Negative pregnancy test for participants of childbearing potential and agreement to use protocoldefined contraception.\n* Ability to understand and sign informed consent\n\nExclusion Criteria:\n\n* Active or untreated CNS metastases, leptomeningeal disease, or uncontrolled seizures.\n* Uncontrolled bacterial, fungal, viral, or mycobacterial infection, including empyema, active pleural space infection, peritonitis, or uncontrolled HBV, HCV, or HIV infection.\n* Autoimmune disease requiring systemic immunosuppression within 14 days before lymphodepletion, or prednisone equivalent greater than 10 mg\u002Fday.\n* Clinically significant cardiovascular disease, uncontrolled arrhythmia, unstable angina, recent myocardial infarction, or other condition judged to increase infusion risk.\n* Severe interstitial lung disease, baseline oxygen requirement, or other pulmonary compromise making pleural therapy unsafe.\n* Bowel perforation risk, uncontrolled bowel obstruction, uncontrolled ascites, or any abdominal condition that makes intraperitoneal infusion unsafe in the peritoneal cohort.\n* Prior gene-modified cell therapy directed against MSLN or FAP within the protocol washout period, or active graft-versus-host disease after prior transplant.\n* Need for concurrent systemic anticancer therapy other than protocol-permitted supportive care.\n* Pregnancy or breastfeeding.\n* Any medical, psychiatric, social, or logistical condition that, in the investigator's judgment, could compromise safety, compliance, or interpretability of study results.",{"count":100,"type":23},[26,27],"This example study evaluates locoregional allogeneic dual-target mesothelin\u002FFAP CAR-NK cells in adults with unresectable, recurrent, or refractory pleural or peritoneal mesothelioma.\n\nEligible participants must have central confirmation of MSLN-positive tumor cells and FAP-positive tumorassociated stroma. The phase 1 portion defines the recommended phase 2 dose and schedule, and the phase 2 expansion explores preliminary antitumor activity, persistence, and biomarker response in pleural and peritoneal disease cohorts.",[554],"Malignant Pleural Mesotheliomas",[556,557,558,199,559,560,561,562],"Mesothelioma","Pleural Mesothelioma","Peritoneal Mesothelioma","FAP","Dual-Target CAR-NK","Locoregional Cell Therapy","Solid Tumor Immunotherapy","2026-03-31",{"date":565,"type":48},"2026-04-06",{"date":50,"type":48},{"date":282,"type":23},{"name":54,"class":55},{"id":570,"slug":571,"hasResults":12,"nctId":572,"briefTitle":573,"officialTitle":574,"acronym":4,"eligibilityCriteria":575,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":576,"targetDuration":4,"studyType":24,"phases":577,"briefSummary":578,"conditions":579,"keywords":583,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":563,"lastUpdatePostDateStruct":589,"startDateStruct":590,"completionDateStruct":591,"leadSponsor":592,"locationsCount":56},"100632216","phase-1-dual-target-car-nk-cells-for-advanced-breast-cancer-her2-tnbc-100632216","NCT07510802","Dual-Target CAR-NK Cells for Advanced Breast Cancer HER2+ TNBC","Phase 1\u002F2, Biomarker-guided, Open-label Study of Allogeneic Dual-target CAR-NK Cells Directed Against HER2\u002FERBB2, MUC1, and\u002For ROR1 in Patients With Advanced or Metastatic Breast Cancer (Including HER2-positive and Triple-negative Disease).","Inclusion Criteria:\n\n* Histologically confirmed breast carcinoma that is locally advanced, unresectable, or metastatic.\n* Disease subtype: HER2-positive breast cancer or triple-negative breast cancer (TNBC).\n* Progression after, intolerance to, or ineligibility for standard therapies appropriate for the disease subtype and line of therapy.\n* At least one measurable lesion per RECIST v1.1.\n* Tumor antigen assessment available (fresh or archival): expression of at least one candidate target antigen (HER2\u002FERBB2, MUC1, or ROR1). For TNBC, mesothelin assessment may be performed for exploratory analyses.\n* ECOG performance status 0-1.\n* Adequate organ function (example thresholds): ANC ≥ 1.0 x 10\\^9\u002FL; platelets ≥ 75 x 10\\^9\u002FL; hemoglobin\n\n  * 8 g\u002FdL; AST\u002FALT ≤ 3x ULN (≤ 5x with liver metastases); total bilirubin ≤ 1.5x ULN; creatinine clearance\n  * 50 mL\u002Fmin.\n* Left ventricular ejection fraction (LVEF) ≥ 45% and no uncontrolled cardiac arrhythmia.\n* Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception during study treatment and for 6 months after last CAR-NK infusion.\n* Ability to understand and willingness to sign informed consent.\n\nExclusion Criteria:\n\n* Active, untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with treated CNS metastases may be eligible if clinically stable for ≥ 4 weeks and off high-dose steroids.\n* Prior gene-modified cellular therapy (e.g., CAR-T or CAR-NK) within 6 months or unresolved grade ≥ 2 toxicity from prior cellular therapy.\n* Clinically significant active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).\n* Uncontrolled infection, including uncontrolled HBV, HCV, or HIV infection (controlled infections may be eligible per investigator).\n* History of severe hypersensitivity to fludarabine or cyclophosphamide.\n* Pregnant or breastfeeding.\n* Concurrent participation in another interventional study that could confound safety or efficacy assessments.\n* Any condition that, in the investigator's judgment, would make the participant unsuitable for the study (e.g., uncontrolled comorbidity, inability to comply with protocol procedures).",{"count":22,"type":23},[26,27],"This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2\u002FERBB2, MUC1, ROR1,TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.",[580,581,582],"Breast Cancer (Advanced\u002FMetastatic)","HER2-positive Breast Cancer","Triple-negative Breast Cancer",[33,224,369,168,200,584,40,37,585,586,587,588],"ROR1","Biomarker-guided cohort assignment","Lymphodepletion","Fludarabine","Cyclophosphamide",{"date":565,"type":48},{"date":349,"type":48},{"date":282,"type":23},{"name":54,"class":55},{"id":594,"slug":595,"hasResults":12,"nctId":596,"briefTitle":597,"officialTitle":598,"acronym":599,"eligibilityCriteria":600,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":601,"targetDuration":4,"studyType":24,"phases":602,"briefSummary":603,"conditions":604,"keywords":606,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":563,"lastUpdatePostDateStruct":609,"startDateStruct":610,"completionDateStruct":611,"leadSponsor":612,"locationsCount":56},"100632218","phase-1-prism-nk-precision-matched-allogeneic-single--or-dual-target-car-nk-cells-for-advanced-solid-tumors-100632218","NCT07510828","PRISM-NK: Precision-Matched Allogeneic Single- or Dual-Target CAR-NK Cells for Advanced Solid Tumors","A Phase 1\u002F2 Biomarker-Guided Platform Study of Allogeneic Donor-Derived Single-Target or Dual-Target CAR-NK Cell Therapy Selected by Tumor Antigen Profiling (Liquid Biopsy and\u002For Tissue Biopsy) in Participants With Advanced Solid Tumors","PRISM-NK","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory to, relapsed after, or intolerant of standard therapy, or for which no standard therapy exists.\n* At least 1 measurable lesion per RECIST v1.1.\n* Tumor antigen positivity documented by tissue biopsy and\u002For liquid biopsy using a protocol-specified assay; for dual-target cohort: co-expression of both antigens above threshold.\n* ECOG performance status 0-1.\n* Adequate organ function (hematologic, renal, hepatic) as defined by protocol labs.\n* Ability to undergo lymphodepleting chemotherapy (if required) and receive IV cell infusion.\n* Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.\n* Willingness to provide baseline blood samples and, when feasible, tumor biopsy for biomarker analyses.\n\nExclusion Criteria:\n\n* Active, uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection.\n* Known uncontrolled HIV infection; active hepatitis B or hepatitis C with evidence of active replication (per local testing).\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk from lymphodepletion or infusion.\n* Active central nervous system (CNS) metastases that are symptomatic or require escalating steroids.\n\n(Stable treated CNS disease may be allowed per protocol.)\n\n* Current systemic immunosuppressive therapy (e.g., \\>10 mg\u002Fday prednisone equivalent) within a protocol-defined window prior to lymphodepletion.\n* Prior gene-modified cellular therapy within 3 months or any prior therapy that, in the investigator's judgment, would confound safety evaluation.\n* Prior allogeneic hematopoietic stem cell transplant within 6 months, or active graft-versus-host disease.\n* Pregnant or breastfeeding.\n* Any condition that, in the investigator's opinion, would interfere with study participation, compliance, or interpretation of results.",{"count":22,"type":23},[26,27],"This Phase 1\u002F2, open-label, biomarker-guided platform study evaluates the safety, tolerability, and preliminary anti-tumor activity of banked allogeneic donor-derived chimeric antigen receptor natural killer (CAR-NK) cells in adults with advanced solid tumors. During screening, tumor antigen profiling is performed using tissue biopsy and\u002For liquid biopsy (circulating tumor DNA and\u002For circulating tumor cells).\n\nParticipants are assigned to receive either a single-target CAR-NK product (matched to the dominant tumor antigen) or a dual-target CAR-NK product (matched to two co-expressed antigens) to reduce the risk of antigen escape.",[605],"Advanced or Metastatic Solid Tumors",[138,144,33,607,608],"mesothelin","tumor",{"date":565,"type":48},{"date":50,"type":48},{"date":282,"type":23},{"name":54,"class":55},{"id":614,"slug":615,"hasResults":12,"nctId":616,"briefTitle":617,"officialTitle":618,"acronym":619,"eligibilityCriteria":620,"healthyVolunteers":12,"sex":18,"minAge":621,"maxAge":622,"enrollmentInfo":623,"targetDuration":4,"studyType":24,"phases":624,"briefSummary":625,"conditions":626,"keywords":631,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":638,"lastUpdatePostDateStruct":639,"startDateStruct":641,"completionDateStruct":642,"leadSponsor":643,"locationsCount":56},"100631561","phase-1-dual-target-gd2b7-h3-car-nk-cells-for-pediatric-relapsed-or-refractory-neuroblastoma-100631561","NCT07502287","Dual-Target GD2\u002FB7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma","A Phase 1\u002FPhase 2, Open-Label Study of BiomarkerInformed, Allogeneic Dual-Target GD2\u002FB7-H3 (CD276) CAR-NK Cells in Children and Young Adults With Relapsed or Refractory Neuroblastoma","DUAL-NK-NB","Inclusion Criteria:\n\n* Age 12 months to 21 years at consent\u002Fassent.\n* Histologically confirmed neuroblastoma or ganglioneuroblastoma with relapsed, refractory, progressive, or persistent high-risk disease for which no curative standard option is available.\n* Measurable or evaluable disease according to revised International Neuroblastoma Response Criteria (rINRC), including MIBG-avid disease, CT\u002FMRI-evaluable soft-tissue disease, and\u002For bone marrow disease.\n* Tumor material available for central assessment of GD2 and B7-H3 expression; at least one target must be positive.\n\nGD2 is treated as the core target and B7-H3 as the complementary target for correlative target-prioritization analyses.\n\n* Prior exposure to standard neuroblastoma therapy, including anti-GD2-based therapy, unless contraindicated, unavailable, or declined for a documented medical reason.\n* Lansky or Karnofsky performance score \\>= 50.\n* Life expectancy \\>= 8 weeks.\n* Recovery from clinically significant acute toxicities of prior therapy and protocol-defined washout from chemotherapy, biologics, radiation, and prior cell therapy.\n* Adequate organ function: hematologic, renal, hepatic, cardiac, and pulmonary function considered sufficient by protocoldefined laboratory and clinical thresholds.\n* Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception during the protocol-defined period.\n* Written informed consent from parent\u002Flegal guardian and assent from the participant when appropriate.\n\nExclusion Criteria:\n\n* Active uncontrolled infection, including bacteremia, uncontrolled viral infection, or invasive fungal disease.\n* Pregnancy or breastfeeding.\n* Active grade \\>= 2 graft-versus-host disease, or systemic immunosuppression for treatment\u002Fprevention of graft-versushost disease within the protocol-defined washout period after prior allogeneic transplant.\n* Symptomatic or unstable central nervous system disease requiring urgent medical intervention.\n* Prior genetically modified cellular therapy within the protocol-defined washout window, or unresolved clinically significant toxicity from prior cell therapy.\n* Active autoimmune disease requiring systemic immunosuppressive therapy.\n* Clinically significant uncontrolled cardiovascular, pulmonary, hepatic, renal, or neurologic disorder that would increase study risk.\n* Known hypersensitivity to fludarabine, cyclophosphamide, study-product components, or supportive-care medications required by the protocol.\n* Known uncontrolled HIV infection or uncontrolled hepatitis B or C.\n* Any medical, psychosocial, or logistical condition that, in the investigator's judgment, would make study participation unsafe or would impair protocol adherence.","12 Months","21 Years",{"count":100,"type":23},[26,27],"This illustrative Phase 1\u002FPhase 2 study tests allogeneic dual-target GD2\u002FB7-H3 (CD276) CAR-NK cells in children and young adults with relapsed or refractory neuroblastoma. After lymphodepletion, participants receive IV CAR-NK cells;Part A defines the RP2D and Part B estimates preliminary activity",[627,628,629,630],"Relapsed Neuroblastoma","Refractory Neuroblastoma","High-Risk Neuroblastoma","Ganglioneuroblastoma",[632,33,140,515,633,634,635,82,636,114,637],"pediatric neuroblastoma","CD276","dual-targeting","relapsed\u002Frefractory","solid tumor immunotherapy","biomarkerinformed design","2026-03-25",{"date":640,"type":48},"2026-03-30",{"date":50,"type":48},{"date":52,"type":23},{"name":54,"class":55},{"id":645,"slug":646,"hasResults":12,"nctId":647,"briefTitle":648,"officialTitle":649,"acronym":650,"eligibilityCriteria":651,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":652,"targetDuration":4,"studyType":24,"phases":653,"briefSummary":654,"conditions":655,"keywords":658,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":663,"lastUpdatePostDateStruct":664,"startDateStruct":665,"completionDateStruct":666,"leadSponsor":667,"locationsCount":56},"100631403","phase-1-dual-target-gpc3b7-h3-car-nk-cells-for-advanced-hcc-100631403","NCT07500220","Dual-Target GPC3\u002FB7-H3 CAR-NK Cells for Advanced HCC","A Phase 1\u002F2, Open-Label, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target GPC3\u002FB7-H3 (CD276) Chimeric Antigen Receptor Natural Killer Cells in Adults With Unresectable, Relapsed\u002FRefractory, or Metastatic Hepatocellular Carcinoma","DUET-HCC","Inclusion Criteria:\n\n* Age 18 to 75 years.\n* Histologically or cytologically confirmed HCC, or radiologically diagnosed HCC with mandatory tissue confirmation of target expression before enrollment.\n* Unresectable, locally advanced, or metastatic HCC not amenable to curative surgery, transplant, or further locoregional therapy; BCLC stage C, or stage B that is not suitable for or has progressed after locoregional therapy.\n* Disease progression on, intolerance to, or ineligibility for at least 1 prior standard systemic regimen.\n* Central pathology showing GPC3 positivity in \\>=25% of viable tumor cells by IHC and B7-H3 positivity in \\>=10% of tumor cells and\u002For tumor-associated stromal\u002Fvascular cells by IHC.\n* At least 1 measurable lesion by RECIST 1.1; intrahepatic lesions must be assessable by contrast-enhanced triphasic CT or MRI.\n* ECOG performance status 0 to 1.\n* Child-Pugh class A or stable Child-Pugh B7 without uncontrolled ascites or recent encephalopathy.\n* Estimated life expectancy \\>=12 weeks.\n* Adequate organ function: WBC \\>=2.5 x 10\\^9\u002FL; platelets \\>=60 x 10\\^9\u002FL; hemoglobin \\>=9 g\u002FdL; serum albumin \\>=30 g\u002FL; creatinine clearance \\>=40 mL\u002Fmin; AST\u002FALT \\\u003C=5 x ULN; total bilirubin \\\u003C=2.5 x ULN; INR\u002Fprothrombin time within protocol-defined range.\n* If HBsAg positive or anti-HBc positive, HBV DNA must be \\\u003C200 IU\u002FmL and the participant must be on appropriate antiviral therapy before lymphodepletion. Controlled HCV is allowed if per protocol.\n* Negative serum pregnancy test for participants of childbearing potential and agreement to effective contraception.\n* Ability to understand and sign informed consent.\n\nExclusion Criteria:\n\n* Prior gene-modified cellular therapy (for example prior CAR-T, CAR-NK, or TCR-engineered therapy) within the protocol-defined washout period or with unresolved clinically significant toxicity.\n* Active, uncontrolled infection, including uncontrolled bacterial, viral, or fungal infection; uncontrolled HIV; active HBV or HCV with uncontrolled viral load; or active tuberculosis.\n* Known active CNS metastases or leptomeningeal disease requiring escalating steroids or urgent local intervention.\n* Liver transplant or other solid-organ transplant history, or current requirement for chronic immunosuppression.\n* Clinically significant ascites requiring frequent drainage, grade \\>=2 hepatic encephalopathy within 4 weeks, or recent clinically significant variceal\u002FGI bleeding.\n* Extensive liver replacement by tumor (for example \\>=70%) or complete major portal vein\u002Fhepatic venous obstruction judged to create excessive treatment risk.\n* Major surgery, locoregional therapy, radiotherapy, or systemic anticancer therapy too close to lymphodepletion per protocol-defined washout period.\n* Active autoimmune disease requiring systemic immunosuppressive therapy, or chronic systemic corticosteroids above protocol threshold.\n* Clinically significant cardiovascular disease (recent myocardial infarction, unstable arrhythmia, uncontrolled heart failure), uncontrolled pulmonary disease, or other serious comorbidity that materially increases study risk.\n* Pregnant or breastfeeding.\n* Any other active malignancy that is progressing or requires current systemic treatment.\n* Any medical or psychiatric condition that, in the investigator's judgment, would compromise safety, protocol compliance, or interpretation of results.",{"count":66,"type":23},[26,27],"open-label trial of an allogeneic dual-target CAR-NK product directed against GPC3 and B7-H3 for adults with advanced hepatocellular carcinoma. The design intentionally uses GPC3 as the primary target anchor because GPC3 is the dominant HCC cell-therapy antigen in current clinical development, while adding B7-H3 to reduce antigen escape and to broaden coverage across tumor and tumor-microenvironment compartments. The study first evaluates safety and dose-limiting toxicities, then expands at the recommended phase 2 dose.",[656,657],"Advanced Hepatocellular Carcinoma (HCC)","Metastatic Liver Cancer",[659,660,661,524,662,515,633,33,109,321,84,114,115,82],"HCC","liver cancer","epatocellular carcinoma","glypican-3","2026-03-24",{"date":640,"type":48},{"date":50,"type":48},{"date":177,"type":23},{"name":54,"class":55},{"id":669,"slug":670,"hasResults":12,"nctId":671,"briefTitle":672,"officialTitle":673,"acronym":674,"eligibilityCriteria":675,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":676,"targetDuration":4,"studyType":24,"phases":677,"briefSummary":678,"conditions":679,"keywords":685,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":692,"lastUpdatePostDateStruct":693,"startDateStruct":694,"completionDateStruct":695,"leadSponsor":696,"locationsCount":56},"100630819","phase-1-dual-target-nectin-4her2-car-nk-cells-in-advanced-urothelial-carcinoma-100630819","NCT07492628","Dual-Target Nectin-4\u002FHER2 CAR-NK Cells in Advanced Urothelial Carcinoma","A Phase 1, Open-Label, Multicenter, Non-Randomized, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target Nectin-4\u002FHER2 CAR-NK Cells Following Fludarabine\u002FCyclophosphamide Lymphodepletion in Adults With Relapsed\u002FRefractory, Locally Advanced or Metastatic Urothelial Carcinoma","DUET-UC-NK","Inclusion Criteria:\n\n* Age 18-75 years at consent.\n* Histologically confirmed urothelial carcinoma of the bladder, ureter, renal pelvis, or urethra that is unresectable locally advanced or metastatic.\n* Disease progression after, intolerance to, or ineligibility for standard therapy, including platinum-based chemotherapy and PD-1\u002FPD-L1 blockade when appropriate for the patient and region. Prior enfortumab vedotin and prior HER2-directed therapy are allowed, but a fresh biopsy is strongly preferred after the latest systemic regimen.\n* At least one measurable lesion per RECIST v1.1.\n* Tumor tissue available for central review demonstrating Nectin-4 positivity (for example, IHC ≥1+ in ≥10% tumor cells) and HER2 status assessed by IHC\u002FISH. At least one of the selected therapeutic targets must be present; dose expansion preferentially enrolls Nectin-4-positive disease.\n* ECOG performance status 0-1.\n* Adequate bone marrow, hepatic, renal, and coagulation function.\n* Life expectancy of at least 12 weeks.\n* Negative pregnancy test for women of childbearing potential and agreement to use highly effective contraception during study treatment and follow-up as defined in the protocol.\n* Ability to understand and sign informed consent.\n\nExclusion Criteria:\n\n* Active or untreated central nervous system metastases or leptomeningeal disease. Previously treated CNS disease is allowed if clinically stable and off escalating corticosteroids.\n* Prior allogeneic hematopoietic stem cell transplant, prior solid-organ transplant, or active graft-versus-host disease.\n* Clinically significant autoimmune disease requiring systemic immunosuppression within the defined washout window.\n* Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, sepsis, or active tuberculosis.\n* Clinically significant cardiac disease, active myocarditis, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful decline in left ventricular ejection fraction that would increase risk from HER2-directed cell therapy.\n* Clinically significant pulmonary disease (for example, uncontrolled interstitial lung disease or oxygen-dependent respiratory compromise).\n* Use of systemic corticosteroids or other immunosuppressive medications above protocol-allowed limits within the washout window.\n* History of severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients.\n* Pregnancy or breastfeeding.\n* Another active malignancy requiring systemic therapy or likely to interfere with protocol assessments, except for protocol-allowed low-risk cancers.",{"count":188,"type":23},[26],"This hypothetical first-in-human study is designed to evaluate the safety, feasibility, and preliminary anti-tumor activity of an allogeneic dual-target Nectin-4\u002FHER2 CAR-NK cell product in adults with relapsed\u002Frefractory locally advanced or metastatic urothelial carcinoma. Based on public urothelial-cancer evidence, Nectin-4 was selected as the lead antigen because it has the strongest disease-specific clinical validation; HER2\u002FERBB2 was chosen as the secondary co-target to broaden tumor coverage and reduce antigen-escape risk. EpCAM is not selected as a therapeutic co-target in this example because of broader normal epithelial expression and weaker tumor specificity in urothelial carcinoma.",[680,681,682,683,684],"Bladder Cancer","Urothelial Carcinoma","Metastatic Urothelial Carcinoma","Locally Advanced Urothelial Carcinoma","Upper Tract Urothelial Carcinoma",[33,138,686,42,77,687,688,109,689,636,690,691],"Nectin-4","urothelial carcinoma","bladder cancer","lymphodepletion","EpCAM","RP2D","2026-03-20",{"date":638,"type":48},{"date":50,"type":48},{"date":256,"type":23},{"name":54,"class":55},{"id":698,"slug":699,"hasResults":12,"nctId":700,"briefTitle":701,"officialTitle":574,"acronym":702,"eligibilityCriteria":575,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":703,"targetDuration":4,"studyType":24,"phases":704,"briefSummary":705,"conditions":706,"keywords":709,"overallStatus":44,"whyStopped":4,"lastUpdateSubmitDate":716,"lastUpdatePostDateStruct":717,"startDateStruct":718,"completionDateStruct":719,"leadSponsor":720,"locationsCount":56},"100630316","phase-1-dual-target-car-nk-cells-for-advanced-breast-cancer-her2-and-tnbc-100630316","NCT07486089","Dual-Target CAR-NK Cells for Advanced Breast Cancer (HER2+ and TNBC)","DUAL-NK-BC",{"count":22,"type":23},[26,27],"This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2\u002FERBB2, MUC1, ROR1, and in some TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.",[707,581,708],"Breast Cancer (Locally Advanced or Metastatic)","Triple-Negative Breast Cancer (TNBC)",[710,711,712,200,584,607,144,713,586,714,715],"CAR-NK; dual targeting","doptive cellular immunotherapy","HER2 \u002F ERBB2","biomarker-guided cohort assignment","fludarabine","cyclophosphamide","2026-03-17",{"date":692,"type":48},{"date":349,"type":48},{"date":177,"type":23},{"name":54,"class":55},""]