Engineered immune cells take on tough bladder cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age 18-75 years at consent. * Histologically confirmed urothelial carcinoma of the bladder, ureter, renal pelvis, or urethra that is unresectable locally advanced or metastatic. * Disease progression after, intolerance to, or ineligibility for standard therapy, including platinum-based chemotherapy and PD-1/PD-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. * At least one measurable lesion per RECIST v1.1. * Tumor tissue available for central review demonstrating Nectin-4 positivity (for example, IHC ≥1+ in ≥10% tumor cells) and HER2 status assessed by IHC/ISH. At least one of the selected therapeutic targets must be present; dose expansion preferentially enrolls Nectin-4-positive disease. * ECOG performance status 0-1. * Adequate bone marrow, hepatic, renal, and coagulation function. * Life expectancy of at least 12 weeks. * 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. * Ability to understand and sign informed consent. Exclusion Criteria: * Active or untreated central nervous system metastases or leptomeningeal disease. Previously treated CNS disease is allowed if clinically stable and off escalating corticosteroids. * Prior allogeneic hematopoietic stem cell transplant, prior solid-organ transplant, or active graft-versus-host disease. * Clinically significant autoimmune disease requiring systemic immunosuppression within the defined washout window. * Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, sepsis, or active tuberculosis. * 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. * Clinically significant pulmonary disease (for example, uncontrolled interstitial lung disease or oxygen-dependent respiratory compromise). * Use of systemic corticosteroids or other immunosuppressive medications above protocol-allowed limits within the washout window. * History of severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients. * Pregnancy or breastfeeding. * Another active malignancy requiring systemic therapy or likely to interfere with protocol assessments, except for protocol-allowed low-risk cancers.