[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"triple-negative-breast-cancer-metastatic\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:triple-negative-breast-cancer-metastatic":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,43,65,78],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100053563","phase-2-a-phase-ii-clinical-study-of-multimodal-ablation-combined-with-systemic-drug-therapy-for-advanced-solid-tumors-100053563",false,"NCT06889610","A Phase II Clinical Study of Multimodal Ablation Combined With Systemic Drug Therapy for Advanced Solid Tumors.","A Single-center,Multi-cohort,Prospective Phase II Clinical Study of Multimodal Ablation Combined With Systemic Drug Therapy for Advanced Solid Tumors.","Inclusion Criteria i. Common eligibility criteria for all cohorts:\n\n1\\. Age between 18-80 years,gender not limited; 2. Patients with hepatic lesions amenable to ablation, all hepatic lesions \\\u003C5 cm in diameter; 3. Expected survival≥3 months; 4. ECOG performance status score of 0-1; 5. Within 14 days before the first dose,laboratory tests indicate adequate organ function:\n\na) Hematology:WBC≥3.0×10\\^9\u002FL;ANC≥1.5×10\\^9\u002FL;PLT≥75×10\\^9\u002FL;HGB≥90 g\u002FL b) Liver function:Child-Pugh score≤7,AST≤5.0×ULN;ALT≤5.0×ULN;TBIL≤1.5×ULN c) Renal function:Cr≤1.5×ULN or CrCl≥60 mL\u002Fmin d) Coagulation function:INR≤1.5×ULN(for patients on anticoagulant therapy,≤3×ULN,anticoagulants must be discontinued one week before ablation);APTT≤1.5×ULN ii. Additional eligibility criteria for each cohort:\n\n1. Colorectal Cancer：\n\n   a) Clinically or pathologically confirmed colorectal cancer with liver metastases that are unresectable, or the patient is intolerant to or refuses surgery; b) Patients who have failed standard second-line drug therapy.\n2. Triple-negative breast cancer :\n\n   1. Clinically or pathologically confirmed triple-negative breast cancer(triple-negative defined as\\\u003C1% nuclear staining for ER and PR expression and HER2 negative);\n   2. Patients who have failed standard second-line drug therapy(including those who have failed PD-1 monoclonal antibody therapy, with progression within six months of adjuvant or neoadjuvant therapy considered as first-line therapy failure).\n3. Melanoma :\n\n   1. Clinically or pathologically confirmed melanoma liver metastasis, with inoperable or intolerable liver lesions or refusal of surgical resection;\n   2. Patients who have failed standard first-line drug therapy.\n\nExclusion Criteria:\n\ni. Common exclusion criteria for all cohorts:\n\n1. Patients with known allergy or suspected allergy to the study drugs or similar drugs;\n2. Patients who have participated in another clinical study and received at least one treatment within 4 weeks prior to enrollment;\n3. History or concurrent presence of other malignant tumors(except for cured basal cell carcinoma of the skin,superficial bladder cancer,carcinoma in situ of the cervix,and papillary thyroid carcinoma);\n4. Patients with immunodeficiency diseases within 7 days prior to the first dose,or currently receiving systemic corticosteroid therapy(≥10mg\u002Fday prednisone or equivalent dose of other corticosteroids),or other forms of immunosuppressive therapy;\n5. Symptomatic central nervous system(CNS)metastases,or other evidence indicating that the CNS metastases have not been controlled,and deemed unsuitable for enrollment by the investigator;\n6. Patients who have previously undergone organ or bone marrow transplantation;\n7. Uncontrollable pleural effusion,pericardial effusion,or ascites causing respiratory syndrome(≥CTCAE grade 2 dyspnea);\n8. Esophageal(gastric fundus)variceal rupture bleeding within the last month;\n9. Other antitumor treatments outside the combined regimen,such as radiotherapy,systemic chemotherapy,etc.;\n10. Clinically significant electrolyte abnormalities as judged by the investigator;\n11. Insufficiency or failure of major organs;\n12. Patients who have received systemic drug therapy,radiotherapy,or local liver treatment,with a time interval of less than 1 month since the last systemic treatment or local liver treatment;\n13. Patients who have received immunotherapy and experienced grade 3 or higher immune-related adverse events(irAEs)(except for thyroid function abnormalities,blood sugar abnormalities);\n14. Active or uncontrolled severe infections(≥CTCAE grade 2 infections);\n15. Any other disease,clinically significant metabolic abnormalities,physical examination abnormalities,or laboratory test abnormalities that,in the investigator's judgment,may have a disease or condition that makes the patient unsuitable for the study drug,or may affect the interpretation of the study results,or may place the patient at high risk;\n16. Pregnant or breastfeeding women,or women of childbearing age with a positive baseline pregnancy test;\n17. Known human immunodeficiency virus(HIV)infection;known clinically significant liver disease history,including viral hepatitis\\[known carriers of hepatitis B virus(HBV)must exclude active HBV infection,i.e.,HBV DNA positive(\\>1×10\\^4 copies\u002FmL or\\>2000 IU\u002FmL);known hepatitis C virus(HCV)infection and HCV RNA positive(\\>1×10\\^3 copies\u002FmL),or other hepatitis,cirrhosis;\n18. Patients with severe heart,lung,liver,or kidney dysfunction,irreversible coagulation disorders,or other uncontrolled diseases(including hypertension or diabetes,active infections,mental illness,or social conditions that may affect patient compliance);\n19. Other factors that may affect patient safety or trial compliance as judged by the investigator.\n\nii. Additional exclusion criteria for each cohort:\n\n1. Colorectal Cancer :\n\n   a) Patients with uncontrolled hypertension, defined as: patients with hypertension that cannot be well-controlled with a single antihypertensive agent (SBP ≥150 mmHg or DBP ≥100 mmHg); or patients who require two or more antihypertensive medications to control blood pressure.\n\n   b）Patients with urine dipstick proteinuria ≥2+ and a 24-hour urinary protein level \\>1.0 g.\n\n   c）Patients with gastrointestinal diseases such as active gastric or duodenal ulcers, ulcerative colitis, or active bleeding from an unresected tumor; or other conditions judged by the investigator as potentially causing gastrointestinal bleeding or perforation.\n\n   d）Patients with evidence or history of a significant bleeding tendency within 3 months prior to enrollment (e.g., bleeding \\>30 mL, hematemesis, melena, hematochezia), hemoptysis (\\>5 mL of fresh blood within 4 weeks), or a thromboembolic event (including stroke and\u002For transient ischemic attack) within the past 12 months.\n\n   e）Patients with clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction, severe\u002Funstable angina, or coronary artery bypass grafting within 6 months prior to enrollment.\n\n   f）Congestive heart failure of New York Heart Association (NYHA) class \\> II; ventricular arrhythmias requiring medication; or an ECG showing a QTc interval ≥480 milliseconds.\n\n   g）Patients who are unable to take fruquintinib orally.\n2. Triple-negative breast cancer :\n\n   a) Patients who have previously received pucotenlimab treatment;\n3. Melanoma :\n\n   1. Patients who have previously received pembrolizumab or toripalimab treatment;\n   2. Patients currently have uncontrolled hypertension,defined as:patients with hypertension that cannot be well controlled with monotherapy(systolic blood pressure≥150 mmHg,or diastolic blood pressure≥100 mmHg);or patients using two or more antihypertensive drugs to control blood pressure;\n   3. Urine routine indicates proteinuria≥2+,and 24-hour urine protein\\>1.0g;\n   4. Significant clinically meaningful cardiovascular diseases,including but not limited to acute myocardial infarction,severe\u002Funstable angina,or coronary artery bypass grafting within 6 months before enrollment;\n   5. Congestive heart failure New York Heart Association(NYHA)classification\\>2;ventricular arrhythmias requiring drug treatment;electrocardiogram(ECG)showing QTc interval≥480 milliseconds.","ALL","18 Years","80 Years",{"count":20,"type":21},95,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This study focuses on the treatment of liver metastases from three common cancers: colorectal cancer, triple-negative breast cancer and melanoma. Currently, there are limitations in the treatment of liver metastases of these cancers. Multimodal thermophysical ablation therapy can reshape the tumor microenvironment, release neoantigens, and act as an in-situ vaccine. On this basis, the combination of multimodal ablation with immunotherapeutic drugs such as pucotenlimab will be explored. The efficacy and safety of this combination therapy in patients with liver metastases of solid tumors will be investigated, with the expectation of breaking through the existing treatment limitations.",[27,28,29],"Triple Negative Breast Cancer Metastatic","Melanoma Metastatic","Colorectal Cancer Metastatic","RECRUITING","2026-07-10",{"date":33,"type":34},"2026-07-13","ACTUAL",{"date":36,"type":34},"2026-03-30",{"date":38,"type":21},"2028-12-30",{"name":40,"class":41},"Fudan University","OTHER",1,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":22,"phases":52,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":55,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":57,"startDateStruct":59,"completionDateStruct":61,"leadSponsor":63,"locationsCount":42},"100624743","phase-2-phase-2-clinical-study-of-iparomlimab-and-tuvonralimab-ql1706-in-combination-with-platinum-chemotherapy-versus-platinum-chemotherapy-in-the-treatment-of-second-third-line-triple-negative-breast-cancer-tnbc-100624743","NCT07413601","Phase 2 Clinical Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Platinum Chemotherapy Versus Platinum Chemotherapy in the Treatment of Second-\u002FThird-line Triple Negative Breast Cancer (TNBC)","Phase 2 Randomized Controlled Clinical Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Platinum Chemotherapy Versus Platinum Chemotherapy in the Treatment of Second-\u002FThird-line Triple Negative Breast Cancer (TNBC)","Inclusion Criteria:\n\n* Age ≥18 years, regardless of gender;\n* ECOG performance status: 0-1;\n* Locally advanced or metastatic triple negative breast cancer confirmed by histopathology that is not suitable for curative treatment and cannot be treated surgically (Defined as negative for HER2, ER and PR expression according to the latest ASCO\u002FCAP guidelines);\n* Patients who have previously received first-line or second-line systemic treatment for locally advanced or metastatic breast cancer and have experienced recurrence within 12 months after the end of previous adjuvant therapy are counted as first-line systemic therapy;\n* There is radiographic or objective evidence of disease progression at the last systemic treatment before or after the start of study treatment;\n* Patients have at least one evaluable lesion (based on CT or MRI according to the RECIST 1.1 criteria);\n* Tissue or blood samples for biomarker testing can be provided, tissue samples during the baseline period (try to provide tumor puncture tissue after recent progression, if not, previously archived tissue is also available, 5-10 white slides); blood samples during the baseline period, after 2 cycles of treatment and after progression;\n* Good organ function：The bone marrow function must be tested within 14 days before enrollment, white blood cell count (WBC) ≥3.5×109\u002FL, hemoglobin (Hb) ≥90g\u002FL, absolute neutrophil count (ANC) ≥1.5×109\u002FL, and platelets (PLT) ≥80×109\u002FL, and have not received blood transfusion or biological response modifiers (such as granulocytes, erythrocyte growth factor, Shengxuebao, etc.) within 14 days before the first dose. Liver function: Liver function must be tested within 14 years before enrollment. Patients without liver metastasis require serum total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Requirements for patients with liver metastases: serum total bilirubin (TBIL) ≤1.5× the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN; alkaline phosphatase (ALP) ≤5×ULN in patients with liver metastases and no bone metastases, and ALP≤2.5×ULN in patients without liver and bone metastases. Renal function: Renal function should be tested within 14 days before enrollment, with blood creatinine ≤1.5×ULN or creatinine clearance ≥60mL\u002Fmin (based on the Cockcroft-Gault formula). No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%(confirmed by ECHO) .Coagulation function: International normalized ratio (INR) ≤1.5×ULN and activated partial thromboplastin time (APTT) ≤1.5×ULN (unless receiving the\\*utic anticoagulant drugs).\n* Patients of childbearing potential must use effective contraceptive measures during the study until 6 months after the last dose.\n* The patient voluntarily joined the study and signed the informed consent form, with good compliance.\n\nExclusion Criteria:\n\n* Previous use of CTLA-4 monoclonal antibody or PD-1\u002FPD-L1 and CTLA-4 bispecific antibodies (such as cardonilumab, KN046, etc.) or bifunctional combination antibodies (e.g., apolitto vorrelizumab);\n* relapse within 6 months after the end of previous (new) adjuvant immune checkpoint inhibitor therapy; or progression-free survival of locally advanced or metastatic breast cancer receiving immune checkpoint inhibitor therapy; 6 months;\n* relapse within 6 months after the end of previous (new) adjuvant platinum therapy; Or locally advanced or metastatic breast cancer receiving platinum therapy has a progression-free survival of \\\u003C3 months (if the drug is discontinued due to non-tumor progression factors, but the duration of discontinuation is ≥3 months before randomization, you can participate in this study);\n* Those who have experienced immune-related toxicity that led to permanent drug discontinuation during previous anti-tumor immunotherapy, or have experienced immune-related adverse events (irAEs) of ≥ grade 3 or immune-related myocarditis of ≥ grade 2 and are assessed by the investigator as not suitable for treatment in this study. Grade 3 endocrine abnormalities with stable control of hormone replacement therapy can be enrolled after the investigator assessed that these irAEs will not affect the administration of study drugs and safety assessment;\n* Previous history of or concurrent interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary dysfunction, symptomatic bronchospasm, etc.;\n* Previous history of other primary malignant tumors; Note: Except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or cervical cancer in situ; Or patients who have received radical treatment and have not relapsed within 5 years of treatment can participate in this trial;\n* Have experienced severe allergic reactions to the pharmaceutical or inactive ingredients of the study drug;\n* Adverse reactions from previous anti-tumor therapy have not recovered to NCI-CTCAE 5.0 grade evaluation ≤1 (Except for toxicities that are judged by the investigator to have no safety risks, such as hair loss);\n* Have active autoimmune disease or have a history of autoimmune disease, are using immunosuppressants, or systemic hormone therapy (prednisone or other equivalent hormone at a dose\\>10mg\u002Fday), and continue to use it within 2 weeks prior to enrollment. Except for the following diseases: Clinically stable autoimmune thyroid disease; Type 1 diabetes treated with hormone replacement therapy; through local treatment (e.g., low-dose topical hormones) are well controlled and no autoimmune skin diseases requiring additional treatment due to acute exacerbation within 12 months prior to screening (such as eczema, psoriasis, chronic lichen simplex, or vitiligo with simple skin lesions accumulating less than 10% of the body surface area);\n* Any serious or uncontrollable systemic disease, including hypertension that is not well controlled with drugs, according to the investigator's judgment (systolic blood pressure\\>160mmHg or diastolic blood pressure\\>100mmHg), uncontrolled diabetes, and signs of active bleeding, etc.;\n* Uncontrolled cardiac disease, including heart failure of NYHA class 2 or above, unstable angina pectoris, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment, prolonged QT syndrome, such as QTc\\>450ms (men) or QTc\\>470ms (women);\n* Evidence of active infection includes but is not limited to hepatitis B (both HBsAg positive and HBVDNA≥2000IU\u002FmL, and hepatitis caused by drugs or other reasons is excluded), hepatitis C (both anti-HCV antibody positive and HCV RNA positive) or human immunodeficiency virus (HIV) infection;\n* Women with positive serum pregnancy tests or nursing do not agree to use adequate contraceptive measures during the study and for 6 months after receiving the trial drug;\n* Subjects with known central nervous system metastases and\u002For cancerous meningitis (except for: asymptomatic, or treatment-treated and stable, no new brain metastases or radiographic evidence of expansion of brain metastases has been found for at least 4 weeks after treatment for brain metastases, and steroid or anticonvulsant treatment has been discontinued for at least 14 days before the start of study treatment);\n* Other circumstances that the investigator deems unsuitable for participation in this clinical trial.",{"count":51,"type":21},78,[24],"This study is an open-label, prospective, phase 2, randomized controlled study to evaluate the efficacy and safety of apolitovorrelizumab (QL1706) in combination with platinum chemotherapy versus platinum chemotherapy in the treatment of advanced unresectable and or metastatic triple negative breast cancer previously treated with first-line or second-line systems. It is planned to enroll 78 subjects in this study. Subjects who meet the inclusion and exclusion criteria are divided into a random ratio of 1:1. The experimental group will receive QL1706 in combination with platinum chemotherapy selected by the investigator, and the control group will receive platinum chemotherapy selected by the investigator. A treatment cycle will be held every 3 weeks until disease progression or intolerable toxicity occurs. After subjects in the control group withdraw from the study, they are allowed to receive other treatments selected by the QL1706 co-investigators based on the subjects 'wishes. Efficacy assessments will be conducted every 6 weeks (42 days ±7 days) after treatment until disease progression, withdrawal of informed consent, death, or start of new antitumor therapy, whichever comes first.",[27],"NOT_YET_RECRUITING","2026-02-09",{"date":58,"type":34},"2026-02-17",{"date":60,"type":21},"2026-02-10",{"date":62,"type":21},"2029-02-10",{"name":64,"class":41},"Cancer Institute and Hospital, Chinese Academy of Medical Sciences",{"id":66,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":67,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":68,"targetDuration":4,"studyType":22,"phases":69,"briefSummary":25,"conditions":70,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":77,"locationsCount":42},"100584459","Inclusion Criteria i. Common eligibility criteria for all cohorts:\n\n1\\. Age between 18-80 years,gender not limited; 2. The number of liver metastases is≥3.Besides the ablation lesions,there must be at least one measurable lesion(≥1cm),and the diameter of the ablation lesions is\\\u003C5cm; 3. Expected survival≥3 months; 4. ECOG performance status score of 0-1; 5. Within 14 days before the first dose,laboratory tests indicate adequate organ function:\n\na) Hematology:WBC≥3.0×10\\^9\u002FL;ANC≥1.5×10\\^9\u002FL;PLT≥75×10\\^9\u002FL;HGB≥90 g\u002FL b) Liver function:Child-Pugh score≤7,AST≤5.0×ULN;ALT≤5.0×ULN;TBIL≤1.5×ULN c) Renal function:Cr≤1.5×ULN or CrCl≥60 mL\u002Fmin d) Coagulation function:INR≤1.5×ULN(for patients on anticoagulant therapy,≤3×ULN,anticoagulants must be discontinued one week before ablation);APTT≤1.5×ULN ii. Additional eligibility criteria for each cohort:\n\n1. Colorectal Cancer：\n\n   a) Clinically or pathologically confirmed colorectal cancer with liver metastases that are unresectable, or the patient is intolerant to or refuses surgery; b) Patients who have failed standard second-line drug therapy.\n2. Triple-negative breast cancer :\n\n   1. Clinically or pathologically confirmed triple-negative breast cancer(triple-negative defined as\\\u003C1% nuclear staining for ER and PR expression and HER2 negative);\n   2. Patients who have failed standard second-line drug therapy(including those who have failed PD-1 monoclonal antibody therapy, with progression within six months of adjuvant or neoadjuvant therapy considered as first-line therapy failure).\n3. Melanoma :\n\n   1. Clinically or pathologically confirmed melanoma liver metastasis, with inoperable or intolerable liver lesions or refusal of surgical resection;\n   2. Patients who have failed standard first-line drug therapy.\n\nExclusion Criteria:\n\ni. Common exclusion criteria for all cohorts:\n\n1. Patients with known allergy or suspected allergy to the study drugs or similar drugs;\n2. Patients who have participated in another clinical study and received at least one treatment within 4 weeks prior to enrollment;\n3. History or concurrent presence of other malignant tumors(except for cured basal cell carcinoma of the skin,superficial bladder cancer,carcinoma in situ of the cervix,and papillary thyroid carcinoma);\n4. Patients with immunodeficiency diseases within 7 days prior to the first dose,or currently receiving systemic corticosteroid therapy(≥10mg\u002Fday prednisone or equivalent dose of other corticosteroids),or other forms of immunosuppressive therapy;\n5. Symptomatic central nervous system(CNS)metastases,or other evidence indicating that the CNS metastases have not been controlled,and deemed unsuitable for enrollment by the investigator;\n6. Patients who have previously undergone organ or bone marrow transplantation;\n7. Uncontrollable pleural effusion,pericardial effusion,or ascites causing respiratory syndrome(≥CTCAE grade 2 dyspnea);\n8. Esophageal(gastric fundus)variceal rupture bleeding within the last month;\n9. Other antitumor treatments outside the combined regimen,such as radiotherapy,systemic chemotherapy,etc.;\n10. Clinically significant electrolyte abnormalities as judged by the investigator;\n11. Insufficiency or failure of major organs;\n12. Patients who have received systemic drug therapy,radiotherapy,or local liver treatment,with a time interval of less than 1 month since the last systemic treatment or local liver treatment;\n13. Patients who have received immunotherapy and experienced grade 3 or higher immune-related adverse events(irAEs)(except for thyroid function abnormalities,blood sugar abnormalities);\n14. Active or uncontrolled severe infections(≥CTCAE grade 2 infections);\n15. Any other disease,clinically significant metabolic abnormalities,physical examination abnormalities,or laboratory test abnormalities that,in the investigator's judgment,may have a disease or condition that makes the patient unsuitable for the study drug,or may affect the interpretation of the study results,or may place the patient at high risk;\n16. Pregnant or breastfeeding women,or women of childbearing age with a positive baseline pregnancy test;\n17. Known human immunodeficiency virus(HIV)infection;known clinically significant liver disease history,including viral hepatitis\\[known carriers of hepatitis B virus(HBV)must exclude active HBV infection,i.e.,HBV DNA positive(\\>1×10\\^4 copies\u002FmL or\\>2000 IU\u002FmL);known hepatitis C virus(HCV)infection and HCV RNA positive(\\>1×10\\^3 copies\u002FmL),or other hepatitis,cirrhosis;\n18. Patients with severe heart,lung,liver,or kidney dysfunction,irreversible coagulation disorders,or other uncontrolled diseases(including hypertension or diabetes,active infections,mental illness,or social conditions that may affect patient compliance);\n19. Other factors that may affect patient safety or trial compliance as judged by the investigator.\n\nii. Additional exclusion criteria for each cohort:\n\n1. Colorectal Cancer :\n\n   a) Patients with uncontrolled hypertension, defined as: patients with hypertension that cannot be well-controlled with a single antihypertensive agent (SBP ≥150 mmHg or DBP ≥100 mmHg); or patients who require two or more antihypertensive medications to control blood pressure.\n\n   b）Patients with urine dipstick proteinuria ≥2+ and a 24-hour urinary protein level \\>1.0 g.\n\n   c）Patients with gastrointestinal diseases such as active gastric or duodenal ulcers, ulcerative colitis, or active bleeding from an unresected tumor; or other conditions judged by the investigator as potentially causing gastrointestinal bleeding or perforation.\n\n   d）Patients with evidence or history of a significant bleeding tendency within 3 months prior to enrollment (e.g., bleeding \\>30 mL, hematemesis, melena, hematochezia), hemoptysis (\\>5 mL of fresh blood within 4 weeks), or a thromboembolic event (including stroke and\u002For transient ischemic attack) within the past 12 months.\n\n   e）Patients with clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction, severe\u002Funstable angina, or coronary artery bypass grafting within 6 months prior to enrollment.\n\n   f）Congestive heart failure of New York Heart Association (NYHA) class \\> II; ventricular arrhythmias requiring medication; or an ECG showing a QTc interval ≥480 milliseconds.\n\n   g）Patients who are unable to take fruquintinib orally.\n2. Triple-negative breast cancer :\n\n   a) Patients who have previously received Pucotenlimab treatment;\n3. Melanoma :\n\n   1. Patients who have previously received Pucotenlimab treatment;\n   2. Patients currently have uncontrolled hypertension,defined as:patients with hypertension that cannot be well controlled with monotherapy(systolic blood pressure≥150 mmHg,or diastolic blood pressure≥100 mmHg);or patients using two or more antihypertensive drugs to control blood pressure;\n   3. Urine routine indicates proteinuria≥2+,and 24-hour urine protein\\>1.0g;\n   4. Significant clinically meaningful cardiovascular diseases,including but not limited to acute myocardial infarction,severe\u002Funstable angina,or coronary artery bypass grafting within 6 months before enrollment;\n   5. Congestive heart failure New York Heart Association(NYHA)classification\\>2;ventricular arrhythmias requiring drug treatment;electrocardiogram(ECG)showing QTc interval≥480 milliseconds.",{"count":20,"type":21},[24],[27,28,29],"2025-11-18",{"date":73,"type":34},"2025-11-21",{"date":75,"type":34},"2025-11-04",{"date":38,"type":21},{"name":40,"class":41},{"id":79,"slug":80,"hasResults":11,"nctId":81,"briefTitle":82,"officialTitle":83,"acronym":84,"eligibilityCriteria":85,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":86,"targetDuration":4,"studyType":22,"phases":88,"briefSummary":89,"conditions":90,"keywords":91,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":106},"100484015","phase-2-restoring-sensitivity-to-immunotherapy-in-advanced-triple-negative-breast-cancer-exploiting-ceralasertib-priming-followed-by-combined-durvalumabnab-paclitaxel-100484015","NCT05582538","Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab\u002FNab-Paclitaxel","Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab\u002FNab-Paclitaxel: The ATRiBRAVE Trial","ATRiBRAVE","Inclusion Criteria:\n\n1. ATRiBRAVE trial written informed consent, prior to any study specific procedures\n2. Age ≥18 years old\n3. Ability to comply with the study protocol in the investigator's judgment.\n4. Ability to swallow and retain oral medication\n5. Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides\n6. Metastatic TNBC patients who have not received prior systemic cytotoxic therapy in the advanced setting and whose tumor have relapsed from treatment with curative intent for early disease, which must have included ICI and chemotherapy as part of radical locoregional therapy\n7. Documented disease progression (e.g., with biopsy sample, pathology or imaging report) since the last treatment in the early setting with curative intent (neo\u002Fadjuvant regimen)\n8. Negative ER\u002FPgR (defined as \\\u003C10% of tumor cells expressing ER and PgR hormonal receptors) and HER2 status (HER2 IHC score 0, 1+ or 2+ non-amplified by in situ hybridization) must be confirmed in the most recent tumor sample (primary and\u002For metastatic)\n9. Evaluable disease, as defined by RECIST 1.1\n10. ECOG performance status 0-1 (refer to Appendix 1)\n11. Patients must have a life expectancy ≥ 3 months from proposed first dose date.\n12. Patients must have acceptable bone marrow, liver and renal functions measured within 28 days prior to administration of study treatment\n13. Body weight \\> 30kg\n14. Women with childbearing potential should complete a pregnancy test with negative result within 28 days of study treatment and be willing to use effective contraceptive methods from screening to 90 days after the last dose of durvalumab\n15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm from screening to 90 days after the last dose of durvalumab.\n\nExclusion Criteria:\n\n1. Diagnosis of ataxia telangiectasia.\n2. Any previous treatment with ATR inhibitors, DNA-damage repair inhibitors.\n3. Patients, who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 therapy:\n\n   1. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.\n   2. All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.\n   3. Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.\n   4. Must not have required the use of additional immunosuppression other than corticosteroids infliximab or Cellcept for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \\> 10 mg prednisone or equivalent per day.\n4. Treatment with any investigational product during the last 28 days before the enrollment.\n5. Patients must have had a washout period of 3 weeks for any prior cancer therapy prior to the start of study drug. The following intervals between the end of the prior treatment and first dose of study drug must be observed: ≥ 4 weeks for radiotherapy (patients who receive palliative radiation for nontarget lesions need not have a 4 week washout period and can be enrolled immediately); patients may receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study; ≥ 4 weeks for major surgery; ≥ 7 days for minor surgical procedures; ≥ 14 days (or 5 half-lives whoever is longest) for any investigational product.\n6. Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of durvalumab, with the exceptions of intranasal, topical, inhaled corticosteroids, and systemic corticosteroids ≤ 10 mg prednisone \u002F day or equivalent.\n7. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≤3 years.\n8. Any gastrointestinal condition that would preclude adequate absorption of ceralasertib, including but not limited to inability to swallow oral medication, refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.\n9. Active or prior documented autoimmune or inflammatory disorders (including IBD \\[e.g. Crohn's disease, ulcerative colitis or diverticulitis\\], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, history of primary immunodeficiency or HIV infection, known hepatitis B or hepatitis C infection, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis within the past 2 years prior to the start of treatment. The following are exceptions to this criterion: i) Subjects with vitiligo or alopecia; ii) hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; iii) any chronic skin condition that does not require systemic therapy; iv) patients with coeliac disease controlled by diet alone and patients without active disease in the last 5 years may be included but only after consultation with the study physician.\n10. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HbsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.\n11. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1\u002F2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).\n12. Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study treatment.\n13. Patients with confirmed COVID-19 infection by PCR test who have not made a full recovery\n14. History of allogeneic organ transplantation.\n15. Untreated central nervous system (CNS) metastatic disease or cord compression. Note: Patients with asymptomatic central nervous system (CNS) metastases are eligible, provided that all of the following criteria are met: (a) The metastases are limited to the supratentorial region or cerebellum (i.e., no metastases to midbrain, pons, medulla, or spinal cord are allowed); (b) No ongoing requirement for corticosteroids as therapy for CNS disease; (c) No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment; (d) Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening imaging study\n16. History of leptomeningeal disease\n17. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia or vitiligo\n18. Resting ECG with measurable QTcF \\> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.\n19. Patients with cardiac problem as follows: uncontrolled hypertension or hypotension (BP ≥150\u002F95 mmHg despite medical therapy, BP \\\u003C90\u002F60 mmHg or orthostatic hypotension fall in BP \\>20 mmHg), Left ventricular ejection fraction \\\u003C55% measured by echocardiography, Atrial fibrillation with a ventricular rate \\>100 bpm on ECG at rest or any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block , third degree heart block, second degree heart block), Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment.\n20. Stroke or transient ischemic attack in the last 6 months prior to screening.\n21. Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites.\n22. Uncontrolled hypercalcemia (\\> 1.5 mmol\u002FL ionized calcium or calcium \\> 12 mg\u002FdL or corrected serum calcium \\> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.\n23. Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.\n24. Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1).\n25. Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive pulmonary disease exacerbation, urinary tract infection or for dental extraction) are eligible.\n26. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases that places the patient at unacceptable risk of toxicity or non-compliance. Examples include, but are not limited to, diabetes type I and II, active bleeding diatheses, renal transplant, uncontrolled seizures, severe COPD, superior vena cava syndrome, extensive bilateral lung disease on High Resolution CT scan, severe Parkinson's disease, refractory nausea or vomiting, irritable bowel syndrome, chronic gastrointestinal disease, significant bowel resection, psychiatric condition, or active infection including any patient known to have tuberculosis, hepatitis B, hepatitis C and human immunodeficiency virus (HIV) or requiring systemic antibiotics, antifungals or antiviral drugs. Screening for chronic conditions is not required.\n27. Concomitant use of known potent cytochrome P (CYP) 3A inhibitors (e.g., ketoconazole,itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to starting study treatment is 2 weeks.\n28. Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.\n29. Receiving or having received, concomitant medications, herbal supplements, and\u002For foods that significantly modulate Pgp activity (washout periods of 5 half-lives).\n30. Known hypersensitivity to ceralasertib, durvalumab or nab-paclitaxel or any of their excipients",{"count":87,"type":21},37,[24],"This study will evaluate the efficacy and safety of ceralasertib followed by durvalumab plus nab-paclitaxel in 37 patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included immunotherapy and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).",[27],[92,93,94,95,96],"immunotherapy","ATR inhibition","ceralasertib","durvalumab","nab-paclitaxel","2025-08-22",{"date":99,"type":34},"2025-08-24",{"date":101,"type":34},"2022-12-15",{"date":103,"type":21},"2029-12",{"name":105,"class":41},"IFOM ETS - The AIRC Institute of Molecular Oncology",6]