Neoadjuvant stereotactic radiotherapy and enfortumab vedotin: A phase I/II study for localized, cisplatin ineligible, muscle invasive bladder cancer (STAR-EV).
Abstract
TPS4623 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. Clinical trial information: NCT06394570 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Tian Zhang
Division of Hematology‐Oncology, Department of Internal Medicine University of Texas Southwestern Medical Center Dallas Texas USA
Solomon L. Woldu
Department of Urology, UT Southwestern Medical Center, Dallas, TX
Minjae Lee
Qian Qin
Suzanne Cole
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Waddah Arafat
Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Changchuan Jiang
Jue Wang
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering
Kevin Dale Courtney
Department of Internal Medicine, Division of Hematology and Oncology, UT Southwestern, Dallas, TX
Andrew DeVilbiss
UT Southwestern Medical Center, Dallas, TX
Molly McGuire
Raquibul Hannan
UT Southwestern Medical Center, Dallas, TX
Daniel X. Yang
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
Aurelie Garant
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
Isamu Tachibana
Department of Urology, UT Southwestern Medical Center, Dallas, TX
Kris Gaston
Department of Urology, UT Southwestern Medical Center, Dallas, TX
Andrew Zhuang Wang
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
Vitaly Margulis
Yair Lotan
Department of Urology, UT Southwestern Medical Center, Dallas, TX
Neil B. Desai
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX