[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"stage-iii-bladder-cancer-ajcc-v8\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:stage-iii-bladder-cancer-ajcc-v8":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,43,71,97],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100641890","phase-1-consolidative-therapy-after-ev--pembrolizumab-in-muscle-invasive-bladder-cancer-reinforce-trial-100641890",false,"NCT07579195","Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial","Consolidative Radiation Therapy or Cystectomy After Initial Favorable Response Succeeding Enfortumab Vedotin Plus Pembrolizumab (REINFORCE)--- A Phase I\u002FII Pilot Feasibility Trial","Inclusion Criteria:\n\n* Age \\>= 18 at the time of screening\n* Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants\n* Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis\n* Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro\n* If M1 after completion of EV + pembro, patients need to have =\\\u003C 5 sites of metastasis and all sites of metastasis should be extracranial\n\n  * Note: when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastatic lesions, etc). Five or fewer sites of metastasis applies after the completion of EV + pembro, not at initial diagnosis\n* Be a candidate for consolidative radiation therapy (RT) to the pelvis (if indicated) or cystectomy (if indicated), and all sites of metastasis are amenable to RT\n* Life expectancy \\> 6 months\n* Eastern Cooperative Oncology Group (ECOG) performance 0-2\n* Absolute neutrophil count (ANC) \\>= 1500 \u002FmcL (within 180 days of trial registration)\n* Platelets \\>= 100,000\u002FmcL (within 180 days of trial registration)\n* Hemoglobin \\> 9 g\u002FdL (within 180 days of trial registration)\n* Creatinine =\\\u003C 1.5 x upper limit of normal (ULN) OR \\>= 60 mL\u002Fmin (within 180 days of trial registration)\n* Total bilirubin =\\\u003C 1.5 ULN OR direct bilirubin =\\\u003C ULN if total bilirubin \\> 1.5 x ULN (within 180 days of trial registration)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 x ULN OR \\\u003C 5 x ULN if patient has live metastasis (within 180 days of trial registration)\n* Albumin \\>= 2.5 g\u002FdL (within 180 days of trial registration)\n* International normalized ratio (INR) or prothrombin time (PT) =\\\u003C 1.5 x ULN unless on anticoagulation therapy, in which case PT or partial thromboplastin time (PTT) should be in the therapeutic range (within 180 days of trial registration)\n* PTT =\\\u003C 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range (within 180 days of trial registration)\n* Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception during, and for at least 90 days after the end of radiation therapy. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours of treatment initiation\n* HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial\n\nExclusion Criteria:\n\n* Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation\n* Intracranial metastasis\n* Any small cell component, or predominant (\\> 50%) sarcomatoid or plasmacytoid histology\n* Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator\n* Genetic conditions that increase sensitivity to radiation, such as Fanconi syndrome, ataxia telangiectasia, and Nijmegen breakage syndrome\n* Active human immunodeficiency virus (HIV) not adequately controlled, active hepatitis B (e.g., hepatitis B virus surface antigen \\[HBsAg\\] reactive) or hepatitis C (e.g., hepatitis C virus \\[HCV\\] ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected)\n* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Any other medical condition that may interfere with trial therapy delivery","ALL","18 Years",{"count":19,"type":20},12,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","This phase I\u002FII clinical trial is evaluating a novel treatment strategy for patients with advanced bladder cancer that is unresectable, has spread to nearby lymph nodes or a limited number of distant sites (oligometastatic disease), and has responded to initial treatment with enfortumab vedotin and pembrolizumab. Although this combination has significantly improved outcomes compared to traditional chemotherapy, many patients are left with residual cancer in the bladder or other sites, and there is currently no established standard approach for managing this remaining disease or determining the optimal duration of systemic therapy. Prolonged treatment can lead to cumulative side effects and negatively impact quality of life.\n\nThis study investigates whether adding consolidative treatment-such as radiation therapy to the bladder and metastatic sites or surgical removal of the bladder (radical cystectomy)-can safely eliminate residual disease and delay cancer progression. Radiation therapy uses high-energy x-rays to precisely target and destroy cancer cells while minimizing exposure to surrounding normal tissues. In selected patients, surgery may be used to remove remaining tumor in the bladder. Targeted radiation techniques, such as stereotactic body radiation therapy (SBRT), may also be used to treat small metastatic sites. This approach may allow for safe discontinuation of systemic therapy, potentially reducing long-term treatment-related side effects.\n\nA key component of this trial is the integration of biomarker testing using circulating tumor DNA (ctDNA) from blood and urine tumor DNA (utDNA). These tests detect small amounts of tumor-derived genetic material and may help identify patients most likely to benefit from consolidative treatment, as well as guide decisions about ongoing therapy. By combining response to systemic therapy with personalized local treatment and biomarker-driven monitoring, this study aims to improve cancer control, reduce complications from untreated local disease, and inform future treatment strategies for patients with advanced bladder cancer.",[27,28,29],"Muscle Invasive Bladder Carcinoma","Stage III Bladder Cancer AJCC v8","Stage IV Bladder Cancer AJCC v8","NOT_YET_RECRUITING","2026-06-17",{"date":33,"type":34},"2026-06-22","ACTUAL",{"date":36,"type":20},"2026-07-01",{"date":38,"type":20},"2029-12-31",{"name":40,"class":41},"University of Washington","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":21,"phases":52,"briefSummary":54,"conditions":55,"keywords":4,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":62,"lastUpdatePostDateStruct":63,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":42},"100574808","phase-4-enfortumab-vedotin-and-pembrolizumab-with-cystectomy-andor-ureterectomy-for-locally-advanced-or-metastatic-bladder-and-upper-urothelial-tract-cancer-cast-ai-trial-100574808","NCT06764095","Enfortumab Vedotin and Pembrolizumab With Cystectomy and\u002For Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial","CAST-AI: Cystectomy After Systemic Therapy With ADC and Immunotherapy","Inclusion Criteria:\n\n* 18 years of age or older at the time of informed consent\n* Histologically proven urothelial carcinoma \\[American Joint Committee on Cancer (AJCC) 2017\\] of the bladder (BCa) or upper urothelial tract (UTUC), N+ and\u002For M+. Initial diagnosis must be within 90 days of planned date for treatment initiation\n\n  * The following variant histologic subtypes are permitted in any amount\n\n    * Urothelial with squamous differentiation\n    * Urothelial with sarcomatoid differentiation\n  * Mixed variant histologic subtypes are permitted if urothelial differentiation is predominant (e.g., \\\u003C 50% variant histologic subtype)\n* Willing to undergo cytoreductive cystectomy (CC) or ureterectomy (U) and deemed clinically a surgical candidate (presuming good response) by the attending urologist\n* Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2\n* Hemoglobin ≥ 8.0 g\u002FdL (obtained ≤ 28 days prior to registration)\n* Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 (obtained ≤ 28 days prior to registration)\n* Platelet count ≥ 80,000\u002Fmm\\^3 (obtained ≤ 28 days prior to registration)\n* Alanine aminotransferase (ALT) OR aspartate transaminase (AST) ≤ 3.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)\n* Total bilirubin ≤ 3 x ULN OR direct bilirubin ≤ 3 x ULN (obtained ≤ 28 days prior to registration)\n* Estimated glomerular filtration rate ≥ 15 ml\u002Fmin (obtained ≤ 28 days prior to registration)\n* Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted, but interval between this treatment and study enrollment must exceed 24 months\n* All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 grade \\\u003C 2 prior to registration\n* Must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study and agree to store samples when applicable\n* Ability to complete questionnaire(s) by themselves or with assistance\n* Willingness to provide mandatory blood specimens for correlative research\n* Willingness to provide tissue specimens for correlative research\n* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)\n\nExclusion Criteria:\n\n* The following histologic variants\u002Fdivergent differentiation are excluded from trial participation:\n\n  * Presence of urothelial carcinoma with histologic variants comprising \\> 50% of histology\n  * Any amount: neuroendocrine, micropapillary, or signet ring cell features\n* Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time (excluding intravesicular therapies)\n* Known active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:\n\n  * Skin cancer (non-melanoma or melanoma) that is considered completely cured\n  * Non-invasive cervical cancer treated that is considered completely cured\n  * Breast cancer:\n\n    * Adequately treated lobular carcinoma in situ or ductal carcinoma in situ considered to have a very low risk of recurrence\n  * Localized prostate cancer (T1c\u002FT2N0M0):\n\n    * Gleason score 6, treated by either surgery or ablation within the last 24 months or untreated and under active surveillance\n    * Gleason score 3+4 that has been treated (may include surgery or ablation) within the last 24 months and considered to have a very low risk of recurrence (i.e., cT1c or pT2 on prostatectomy specimen)\n* Received prior systemic chemotherapy or targeted small molecule therapy (excluding hormonal therapy) within 2 years prior to starting study treatment\n* History of uncontrolled adrenal insufficiency\n* History of uncontrolled cardiovascular disease including any of the following in the preceding 6 months: unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive New York Heart Association class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; pulmonary embolism or other venous thromboembolism\n* Known active tuberculosis\n* Is receiving immunosuppression for an allogeneic tissue\u002Fsolid organ transplant\n* Participants with an active autoimmune disease requiring systemic treatment. Participants with autoimmune disorders not requiring systemic treatment (eg, skin conditions such as vitiligo or alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll\n* Known clinically significant liver disease that precludes participant treatment regimens prescribed on the study (including, but not limited to active viral, alcoholic, or other autoimmune hepatitis, cirrhosis, or inherited liver disease)\n* Known human immunodeficiency virus (HIV) infection, unless the participant has been on a stable antiretroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of \\> 350 in the last 6 months\n* Known active hepatitis B or C infection \\[however, participants with history of hepatitis C infection but normal hepatitis C virus polymerase chain reaction test and participants with hepatitis B with positive hepatitis B surface antigen (HBsAg) antibody are allowed\\]\n* Known urinary tract infection (UTI), defined as a symptomatic infection with a positive urine culture with a bacterial count of ≥ 10\\^5 colony forming units (CFU)\u002FmL in urine voided from women, or \\> 104 CFU\u002FmL in urine voided from men, or in straight catheter urine from women. Symptoms may include dysuria, urgency, frequency, and\u002For systemic symptoms such as fever, chills, elevated white blood cell, and\u002For abdominal\u002Fflank pain. Participants free from symptoms for 7 days with no culture evidence of ≥ 10\\^5 CFUs may be eligible\n* Known active, uncontrolled urogenital bacterial, viral or fungal infections, including UTI. Skin\u002Fnail fungal infections are not exclusionary. Participants with active shingles (varicella zoster infection) will be excluded from the study\n* Evidence of interstitial lung disease or active non-infectious pneumonitis\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Participants who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation\n* Known history of impaired wound healing capacity defined as skin\u002Fdecubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions\n* Pelvic radiotherapy administered at any time\n* Received a live virus vaccine within 30 days of planned start of study treatment\n* Active autoimmune disease that has required systemic treatment in the past 2 years\n* Active infection requiring systemic intravenous therapy within 30 days prior to planned treatment initiation\n* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways\n* Participants with a history of grade ≥ 3 toxic effects when using anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-6 agents are excluded\n* Participants still recovering from toxicity of prior anticancer therapy which was received more than 24 months prior to enrollment (except toxicities which are not clinically significant such as alopecia, skin discoloration)\n* Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses \\> 10 mg\u002Fday of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF alpha blockers. Use of immunosuppressive medications for the management of immune related adverse events, infusion related reactions, or in participants with contrast allergies is acceptable. Use of inhaled, topical, and intranasal corticosteroids are permitted\n* Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune mediated thrombocytopenia or anemia) are excluded\n* Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment\n* Participants who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before registration \\[transurethral resection of bladder tumor (TURBT) is not considered major surgery\\]. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate\n* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception\n* Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participants (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments\n* The participant is unable to comply with the requirements of this protocol, including any factors that are likely to affect the participant's return for scheduled visits and follow-up",{"count":51,"type":20},75,[53],"PHASE4","This phase IV trial tests the impact of standard of care enfortumab vedotin and pembrolizumab followed by removal of all or part of the bladder (cytoreductive cystectomy) and\u002For removal of all or part of the tube that carriers urine from the kidneys to the bladder (ureterectomy) on outcomes in patients with bladder and upper urothelial tract that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving standard of care enfortumab vedotin and pembrolizumab followed by cytoreductive cystectomy and\u002For ureterectomy (CC\u002FU) may improve outcomes in patients with locally advanced or metastatic bladder or upper urothelial tract cancer.",[56,57,58,59,28,29,60],"Locally Advanced Bladder Urothelial Carcinoma","Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma","Metastatic Bladder Urothelial Carcinoma","Metastatic Renal Pelvis and Ureter Urothelial Carcinoma","Stage IV Renal Pelvis and Ureter Cancer AJCC v8","RECRUITING","2026-02-10",{"date":64,"type":34},"2026-02-12",{"date":66,"type":34},"2025-01-08",{"date":68,"type":20},"2034-12-31",{"name":70,"class":41},"Mayo Clinic",{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":4,"eligibilityCriteria":77,"healthyVolunteers":78,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":79,"targetDuration":4,"studyType":21,"phases":81,"briefSummary":83,"conditions":84,"keywords":4,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":95,"locationsCount":42},"100547926","an-education-and-navigation-support-tool-to-improve-participation-in-care-coordination-among-patients-with-locally-advanced-metastatic-and-unresectable-bladder-cancer-and-their-caregivers-100547926","NCT06414317","An Education and Navigation Support Tool to Improve Participation in Care Coordination Among Patients With Locally Advanced, Metastatic and Unresectable Bladder Cancer and Their Caregivers","A Comprehensive Education and Navigational Support Program for Advanced Bladder Cancer","Inclusion Criteria:\n\n* PATIENTS: Age ≥ 18 years\n* PATIENTS: Metastatic or locally advanced, unresectable bladder cancer\n* PATIENTS: Receiving or planning to receive systemic therapy for bladder cancer at Roswell Park Comprehensive Cancer Center (RPCCC)\n* PATIENTS: Subjects can be enrolled any time from initial diagnosis of advanced disease to within 8 weeks after initiation of first-line systemic therapy for advanced bladder cancer\n* PATIENTS: Able to speak, understand, read, and write English\n* CAREGIVERS: Age ≥ 18 years\n* CAREGIVERS: Only caregivers of enrolled patients will be included in the study\n* CAREGIVERS: Should be able to speak, understand, read, and write English\n* CAREGIVERS: Caregivers will be enrolled in the study during the same time window as for patient enrollment (from initial visit to within 8 weeks of patients starting frontline therapy)\n\nExclusion Criteria:\n\n* PATIENTS: Not receiving any form of systemic therapy for bladder cancer due to Eastern Cooperative Oncology Group (ECOG) performance status (PS) \\> 3, co-morbidities, or inadequate organ function\n* PATIENTS: Predominantly small cell histology\n* PATIENTS: Adults with impaired decision-making capacity, assessed by the study team to be unable to participate in ENST-based education and surveys\n* PATIENTS: Pregnant women\n* CAREGIVERS: Cognitively impaired adults\u002Fadults with impaired decision-making capacity\n* CAREGIVERS: Individuals who are not yet adults (infants, children, teenagers)",true,{"count":80,"type":20},160,[82],"NA","This clinical trial evaluates the impact of an education and navigation support tool (ENST) on patient and caregiver participation in care coordination for bladder cancer that has spread to nearby tissue or lymph nodes (locally advanced), to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Patients with advanced bladder cancer tend to be older, have multiple medical conditions and often have poor access to health care. An ENST may be an effective method to improve participation in treatment decision-making and care planning among patients with locally advanced, metastatic and unresectable bladder cancer and their caregivers.",[85,86,28,29,87],"Locally Advanced Bladder Carcinoma","Metastatic Bladder Carcinoma","Unresectable Bladder Carcinoma","2026-01-27",{"date":90,"type":34},"2026-01-29",{"date":92,"type":34},"2024-01-12",{"date":94,"type":20},"2027-03-31",{"name":96,"class":41},"Roswell Park Cancer Institute",{"id":98,"slug":99,"hasResults":11,"nctId":100,"briefTitle":101,"officialTitle":102,"acronym":4,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":104,"targetDuration":4,"studyType":21,"phases":106,"briefSummary":107,"conditions":108,"keywords":4,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":115,"lastUpdatePostDateStruct":116,"startDateStruct":118,"completionDateStruct":120,"leadSponsor":122,"locationsCount":5},"100497386","phase-2-enfortumab-vedotin-plus-pembrolizumab-for-the-treatment-of-locally-advanced-or-metastatic-bladder-cancer-of-variant-histology-100497386","NCT05756569","Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology","Phase II Single-Arm Study of Enfortumab Vedotin (EV) Plus Pembrolizumab in the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology","Inclusion Criteria:\n\n* Male or Female\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%)\n* Metastatic disease or unresectable locally advanced disease\n* Histologically documented variant histology (nested, microcytic, micropapillary, lymphoepithelioma-like, plasmacytoid, giant cell, poorly differentiated, lipid-rich, clear cell, sarcomatoid) bladder cancer and non-urothelial bladder cancer of epithelial origin including squamous cell carcinoma and adenocarcinoma (urachal and non-urachal). Variant histology tumors and non-urothelial tumors of ureter, urethra, urachus, or renal pelvis are included. Patients with mixed cell type are eligible if the predominant histology (over 50%) is variant or non-urothelial. All histological classifications will follow the 2016 WHO Classifications.\n* Untreated or having received any number of lines of prior therapy\n* Tumor tissue samples must be available for submission prior to initiation of study treatment. If not, agree to undergo biopsy\n* Patients must have measurable disease as defined by RECIST criteria 1.1 as at least one lesion that can be accurately measured in at least one dimension (longest diameter of \\>= 10 mm for non-nodal lesions or short axis of \\>= 15 mm for nodal lesions) on CT scan, MRI\n* Patients must have adequate organ and marrow function, within 28 days of cycle 1 day 1, at the discretion of the investigator\n* The effects of study drugs on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy\n* FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Additionally, FCBP and male subjects should use effective contraception for 6 months after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male subjects must not donate sperm and female subjects must not donate ova from screening to 6 months after the last dose\n* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer \\>= 4 weeks before the start of study therapy\n* Life expectancy \\> 12 weeks as determined by the Investigator\n* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions\n* Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation\n\nExclusion Criteria:\n\n* The neuroendocrine histology (small cell and large cell carcinomas) and non-epithelial bladder tumors (e.g. bladder sarcoma, carcinosarcoma, paraganglioma, melanoma, primary lymphoma, and lymphoepithelioma-like carcinoma) are excluded.\n* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier \\[i.e. ongoing clinically significant toxicity (grade 2 or higher with the exception of alopecia) associated with prior treatment\\]\n* Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study\n* Patients with ongoing sensory or motor neuropathy grade \\>= 2\n* Prior treatment or enrollment in a study with EV or PD1\u002FPD-L1 immune checkpoint inhibitor (including maintenance therapy)\n* Known uncontrolled diabetes mellitus with glycated hemoglobin (HbA1c) \\>= 8% or HbA1c 7% to \\\u003C 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained\n* Active central nervous system (CNS) metastases\n* Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for localized prostate cancer, definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months\n* Currently receiving systemic antimicrobial treatment for active infection or high dose steroids (\\> 10mg of prednisone or equivalent)\n* A FCBP who has a positive urine pregnancy test at baseline or within 72 hours prior to receiving first study dose. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Breastfeeding females\n* History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), known hepatitis B (defined as hepatitis B surface antigen \\[HBsAg\\] reactive), known active hepatitis C virus (defined as HCV ribonucleic acid \\[mRNA\\] \\[qualitative\\] is detected) or tuberculosis\n* History of active keratitis or corneal ulcerations\n* History of allogenic tissue\u002Fsolid organ transplant\n* Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 6 months prior to first dose of EV\u002Fpembrolizumab\n* Other uncontrolled current illness including, but not limited to, cardiac arrhythmia or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements",{"count":105,"type":20},25,[24],"This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.",[109,85,110,111,112,86,28,29,87,113,114],"Bladder Squamous Cell Carcinoma","Malignant Renal Pelvis Neoplasm","Malignant Ureter Neoplasm","Malignant Urethral Neoplasm","Urachal Adenocarcinoma","Bladder Adenocarcinoma","2025-07-24",{"date":117,"type":34},"2025-07-28",{"date":119,"type":34},"2023-09-26",{"date":121,"type":20},"2027-12-16",{"name":123,"class":41},"Emory University"]