STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Urothelial carcinoma of the urinary bladder stage cT1-4a (AJCC 8th edition) N0M0 planned for radical cystectomy.
For cR1 staged patients. the patient must have high grade disease AND be appropriate for cystectomy.
Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
Age >=18.
No prior systemic therapy (except prior therapy for non-muscle invasive bladder cancer >12 prior to registration) for bladder cancer or prior pelvic radiotherapy. Prior intra-vesical therapies are allowed, including Bacillus Calmette-Guerin (BCG) for non-muscle invasive bladder cancer. Prior chemotherapy for other cancers is allowed if given >=1 year prior to study registration.
Baseline >= Grade 2 sensory or motor neuropathy
Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other agents used in study.
Sequential
Enfortumab vedotin
DrugEnfortumab Vedotin administered 1.25mg/kg (max 125mg) IV on Day 1 and Day 8 of each 21 day cycle x 3 cycles
Maximum Tolerated Dose (MTD) Regimen
A standard 3 + 3 dose escalation schedule will be used for all escalations. Enfortumab Vedotin will be given for three 21 day cycles. Radiation therapy will be administered at dose level 0, level 1 or level 2.
Pathologic Complete response rate at radical cystectomy
Rate of complete pathologic response in bladder tumor biopsy at cystectomy according to postsurgical staging.
Adverse Events
Adverse events reported and observed according to CTCAE v5.0
Rate of pathologic downstaging in the bladder
Rate of post surgical pathologic staging being less than clinical staging.
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University of Texas Southwestern Medical Center
Lead sponsor
Astellas Pharma Inc
Collaborator
