Circulating Tumor DNA Response In Urothelial Cancer

Prior treatment

• Previously received enfortumab, vedotin, or other monomethyl auristatin E (MMAE)-based ADCs.
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage UC, defined as a PD-1 inhibitor or PD-L1 inhibitor within 12 months.
• Has received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed within 28 days prior to cycle 1 day 1.
• Experiences ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline.
• Is currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal). Routine antimicrobial prophylaxis is permitted.
• Received radiotherapy within 2 weeks.
• Received major surgery (defined as requiring general anesthesia and \>24-hour inpatient hospitalization) within 2 weeks.
• Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
  • Participants that received neoadjuvant chemotherapy with recurrence \>12 months from completion of therapy are permitted.
  • Participants that received adjuvant chemotherapy or ICPIs therapy following cystectomy with recurrence \>12 months from completion of therapy are permitted.
• Has received prior allogeneic stem cell or solid organ transplant.
• Received a live attenuated vaccine within 30 days.

Other illness

• Has uncontrolled diabetes or ≥ grade III peripheral neuropathy.
• Has known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• Has history of another invasive malignancy requiring treatment within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy (excluding localized prostate cancer or basal cell carcinoma of skin or squamous cell carcinoma of the skin).
• Has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months.
• Known severe (≥ Grade 3) hypersensitivity to any EV excipient contained in the drug formulation of EV.
• Has a history of autoimmune disease that has required systemic immunosupressive treatment in the past 2 years, or uncontrolled autoimmune disease.
• Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.

Other

• Patient's estimated life expectancy is less than 12 weeks.
• Has untreated central nervous system metastases.
• Has active keratitis or corneal ulcerations.

• Have histologically documented unresectable, locally advanced, or metastatic urothelial carcinoma.
• Measurable disease according to the New Response Evaluation Criteria in Solid Tumors (RECIST v1.1)38
  • Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy.
• Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment.
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma must be available for tumor-informed ctDNA analysis.
• Meets Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2.
• Adequate hematologic and organ function (Hb ≥ 8.0 g/dL; ANC ≥ 1.5x109 cells/L; CrCl \~30 mL/min; total bilirubin ≤ 1.5 mg/dL; ALT and AST within normal limits).