Enfortumab Vedotin and Pembrolizumab for Advanced Bladder and Upper Urothelial Cancer
This study, called CAST-AI, is testing a treatment plan for locally advanced or metastatic bladder and upper urothelial tract cancer. You might be eligible if you are 18 or older and have been recently diagnosed with this type of cancer. The treatment involves two drugs, enfortumab vedotin and pembrolizumab, followed by surgery to remove all or part of your bladder (cystectomy) and/or the tube carrying urine from your kidneys (ureterectomy). Enfortumab vedotin is a targeted drug that helps stop tumor growth, and pembrolizumab is an immunotherapy that helps your immune system fight cancer. The main goal is to see how many people are still alive and free from cancer progression after 12 months. The study is planning to enroll 75 participants, but its current recruitment status is unclear.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It aims to enroll 75 participants.
- What's involved
- You would undergo urine and blood sample collection, CT or PET/CT scans, and receive enfortumab vedotin and pembrolizumab intravenously. You would also undergo cystectomy and/or ureterectomy.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study measures progression-free survival at 12 months, suggesting follow-up for at least that duration.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06764095
Enfortumab Vedotin and Pembrolizumab With Cystectomy and/or Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial
Recruiting
PHASE4Ages 18+InterventionalTreatmentMayo ClinicInvestigator-initiated
~75 participants
Updated 2026-02-12 on ClinicalTrials.gov
What's tested:Biospecimen CollectionComputed TomographyCystectomyEnfortumab VedotinLocal TherapyMagnetic Resonance Imaging
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-free survival (PFS) at 12 months
Measured over At 12 months
Conditions
NCT06764095
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Mayo Clinic in Rochester
Rochester, Minnesotastudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Jacob J. Orme, MD, PhD · PRINCIPAL_INVESTIGATOR · Mayo Clinic in Rochester
- Paras H. Shah, MD · PRINCIPAL_INVESTIGATOR · Mayo Clinic in Rochester
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Want this trial checked against your situation?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
18 years of age or older at the time of informed consent
Histologically proven urothelial carcinoma \[American Joint Committee on Cancer (AJCC) 2017\] of the bladder (BCa) or upper urothelial tract (UTUC), N+ and/or M+. Initial diagnosis must be within 90 days of planned date for treatment initiation
The following variant histologic subtypes are permitted in any amount
Urothelial with squamous differentiation
Urothelial with sarcomatoid differentiation
Mixed variant histologic subtypes are permitted if urothelial differentiation is predominant (e.g., \< 50% variant histologic subtype)
Willing to undergo cytoreductive cystectomy (CC) or ureterectomy (U) and deemed clinically a surgical candidate (presuming good response) by the attending urologist
Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2
Hemoglobin ≥ 8.0 g/dL (obtained ≤ 28 days prior to registration)
Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 28 days prior to registration)
Platelet count ≥ 80,000/mm\^3 (obtained ≤ 28 days prior to registration)
Alanine aminotransferase (ALT) OR aspartate transaminase (AST) ≤ 3.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)
Total bilirubin ≤ 3 x ULN OR direct bilirubin ≤ 3 x ULN (obtained ≤ 28 days prior to registration)
Estimated glomerular filtration rate ≥ 15 ml/min (obtained ≤ 28 days prior to registration)
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
All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 grade \< 2 prior to registration
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
Ability to complete questionnaire(s) by themselves or with assistance
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide tissue specimens for correlative research
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Exclusion
The following histologic variants/divergent differentiation are excluded from trial participation:
Presence of urothelial carcinoma with histologic variants comprising \> 50% of histology
Any amount: neuroendocrine, micropapillary, or signet ring cell features
Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time (excluding intravesicular therapies)
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:
Skin cancer (non-melanoma or melanoma) that is considered completely cured
Non-invasive cervical cancer treated that is considered completely cured
Breast cancer:
Adequately treated lobular carcinoma in situ or ductal carcinoma in situ considered to have a very low risk of recurrence
Localized prostate cancer (T1c/T2N0M0):
Gleason score 6, treated by either surgery or ablation within the last 24 months or untreated and under active surveillance
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)
Received prior systemic chemotherapy or targeted small molecule therapy (excluding hormonal therapy) within 2 years prior to starting study treatment
History of uncontrolled adrenal insufficiency
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
Known active tuberculosis
Is receiving immunosuppression for an allogeneic tissue/solid organ transplant
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
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)
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
Known active hepatitis B or C infection \[however, participants with history of hepatitis C infection but normal hepatitis C virus polymerase chain reaction test and participants with hepatitis B with positive hepatitis B surface antigen (HBsAg) antibody are allowed\]
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)/mL in urine voided from women, or \> 104 CFU/mL in urine voided from men, or in straight catheter urine from women. Symptoms may include dysuria, urgency, frequency, and/or systemic symptoms such as fever, chills, elevated white blood cell, and/or abdominal/flank pain. Participants free from symptoms for 7 days with no culture evidence of ≥ 10\^5 CFUs may be eligible
Known active, uncontrolled urogenital bacterial, viral or fungal infections, including UTI. Skin/nail fungal infections are not exclusionary. Participants with active shingles (varicella zoster infection) will be excluded from the study
Evidence of interstitial lung disease or active non-infectious pneumonitis
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
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
Known history of impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions
Pelvic radiotherapy administered at any time
Received a live virus vaccine within 30 days of planned start of study treatment
Active autoimmune disease that has required systemic treatment in the past 2 years
Active infection requiring systemic intravenous therapy within 30 days prior to planned treatment initiation
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
Participants with a history of grade ≥ 3 toxic effects when using anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-6 agents are excluded
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)
Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses \> 10 mg/day 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
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
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
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
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
Pregnant persons
Nursing persons
Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
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
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
What this trial measures
- Progression-free survival (PFS) at 12 monthsAt 12 months
Will be calculated as the number of patients who are alive and progression-free at 12 months after study enrollment. Progression will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria.