(UroToday.com) The 2025 Western Section AUA annual meeting featured a urothelial carcinoma session and a presentation by Dr. Siamak Daneshmand discussing PIVOT-006, an ongoing phase 3, randomized study of adjuvant intravesical cretostimogene grenadenorepvec versus surveillance for the treatment of intermediate risk non-muscle invasive bladder cancer.
The AUA/SUO guidelines recommend adjuvant intravesical therapy or surveillance for intermediate-risk non-muscle invasive bladder cancer. Despite this, up to 60% of patients will recur, highlighting a need for improved therapies. With real-world data suggesting a lack of adjuvant chemotherapy use, surveillance is the most appropriate real-world comparator for clinical trials.
Cretostimogene grenadenorepvec, an oncolytic immunotherapy, selectively replicates in and lyses cancer cells with Rb-E2F pathway alterations, releasing antigens that initiate antitumor immune activation, further amplified by the GM-CSF transgene:
Cretostimogene received US FDA Fast Track and Breakthrough Designations for high-risk, BCG-unresponsive non-muscle invasive bladder cancer with CIS and has shown a favorable safety profile. The PIVOT-006 (NCT06111235) phase 3 study is designed to assess the efficacy and safety of adjuvant cretostimogene versus surveillance in patients with intermediate risk non-muscle invasive bladder cancer.
Eligibility criteria for PIVOT-006 include a histologically confirmed intermediate risk non-muscle invasive bladder cancer diagnosis within 90 days of randomization, as defined by AUA/SUO guidelines. Stratification factors include receipt of single-dose perioperative chemotherapy and tumor grade. Patients (n ~ 364) will be randomized 1:1 to undergo surveillance or to receive intravesical cretostimogene following TURBT. If intermediate risk non-muscle invasive bladder cancer recurrence is noted in the surveillance arm, patients will be eligible to receive intravesical cretostimogene:
Intravesical cretostimogene is administered in combination with n-dodecyl-β-D-maltoside (DDM), an excipient that enhances adenoviral delivery, for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in a single intravesical dose at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples:
The primary endpoint is recurrence-free survival, and secondary outcomes include safety, tolerability, progression-free survival, and time to next intervention. Exploratory outcome measures include health-related quality of life and biomarker analyses. PIVOT-006 represents one of the first randomized controlled trials in intermediate risk non-muscle invasive bladder cancer and has received SUO-Clinical Trials Consortium (SUO-CTC) and Bladder Cancer Advocacy Network support. 90+ clinical sites, including diverse representations across private practice and academic institutions, were selected for the trial. Enrollment for PIVOT-006 is complete.
Presented by: Siamak Daneshmand, MD, Professor of Urology and Medicine (Clinical Scholar), Director of Urologic Oncology and Clinical Research, Keck School of Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Western Section American Urological Association (AUA) Annual Meeting, Napa Valley, CA, Sun, Nov 2 – Thurs, Nov 6, 2025.