Neoadjuvant stereotactic radiotherapy and enfortumab vedotin: A phase I/II study for localized, cisplatin ineligible, muscle invasive bladder cancer (STAR-EV).
Background:
Patients with muscle invasive bladder cancer (MIBC) may not be candidates for cisplatin-based chemotherapy based on their comorbidities and clinical status. Based on EV-103 cohort H, patients with localized, cisplatin ineligible MIBC respond well to enfortumab vedotin (EV), with 36% pathologic complete responses (pCRs). Radiation (XRT) is also an effective therapy for MIBC, with recent retrospective data showing safety when combining XRT-EV. Therefore, we designed a trial with EV and XRT to improve pCR rates.
Methods:
STAR-EV is a single center, phase 1/2 trial open at UT Southwestern Medical Center. Patients will receive EV 1.25mg/m2 IV days 1/8 every 3 weeks for 3 cycles, with either sequential or concurrent stereotactic body XRT (SBRT) in 5 fractions. The safety lead-in phase starts with SBRT given at cycle 3 day 21 and then escalated forward to start at cycle 2 day 15 (level 1) or cycle 1 day 15 (level 2). All patients undergo radical cystectomy (RC). Dose limiting toxicities during the safety portion include non-hematologic adverse events grade 3 or higher, not completing 3 cycles of EV, delaying SBRT over 2 weeks, or delaying RC over 8 weeks. Rate of pCR is the primary endpoint for efficacy, with a goal of 60% pCR. In a Simon’s two-stage design, if more than 3 pCRs are seen in the first 8 patients, 11 additional patients will be enrolled (total n = 19). The null hypothesis will be rejected if more than 10 pCRs are found.
Main inclusion criteria include urothelial cancer of the bladder, cT2-4aN0M0, > 50% urothelial histology, and cisplatin ineligible; main exclusion criteria include any small cell/neuroendocrine histology, prior systemic therapy for bladder cancer, prior pelvic XRT, baseline grade 2 or higher neuropathy, prior allergic reaction attributed to EV, or uncontrolled intercurrent illness. Secondary endpoints include safety of combining EV and SBRT, rate of pathologic down-staging; and exploratory objectives include quality of life, disease free survival after RC, and delay of RC > 8 weeks from end of EV/SBRT. Serum and urinary biomarkers will be explored. The study is open and enrolling (NCT06394570).
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Author Details
Tian Zhang
Department of Internal Medicine, Division of Hematology and Oncology, UT Southwestern, Dallas, TX
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Genitourinary Cancer—Kidney and Bladder
Track
Genitourinary Cancer—Kidney and Bladder
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