(UroToday.com) The 2022 Society of Urologic Oncology annual meeting featured a session on bladder cancer, including a presentation by Christine Lentowski discussing the trial design of a phase 3 single-arm study of UGN-102 as primary chemoablative therapy in patients with low grade intermediate risk non-muscle invasive bladder cancer. UGN-102 is a mitomycin-containing reverse thermal gel in development for primary nonsurgical treatment of low grade intermediate risk non-muscle invasive bladder cancer.
Patients with low grade intermediate risk non-muscle invasive bladder cancer are currently treated with transurethral resection of bladder tumors (TURBT), usually under general anesthesia. However, there is no approved medicinal product for primary treatment. A subset of patients with low grade non-muscle invasive bladder cancer (intermediate risk population) experience repeated recurrence of tumors requiring repetitive TURBT, which is associated with postoperative and long-term morbidity and an increased mortality risk.
This phase 3 study is designed to confirm the results of a phase 2b single-arm study in patients with low grade intermediate risk non-muscle invasive bladder cancer, in which 41/63 (65%) patients achieved the primary endpoint of complete response at 3 months, and 25/41 (61%) patients had a durable complete response at 12 months after the start of treatment. The probability of durable response 9 months after complete response was estimated to be 73% by Kaplan-Meier analysis.1
For the current trial, approximately 220 patients with a history of low grade non-muscle invasive bladder cancer and prior TURBT who meet intermediate risk disease criteria will receive 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin). Key inclusion criteria include:
- Patients who have Ta non-muscle invasive bladder cancer confirmed by cold cup biopsy at screening or within 8 weeks before screening
- Any history of low grade non-muscle invasive bladder cancer
- Patients with intermediate risk disease, defined as any of the following:
- Presence of multiple tumors
- Solitary tumor > 3 cm
- Early or frequent recurrence (>= 1 recurrence of low grade non-muscle invasive bladder cancer within 1 year of the current diagnosis at the initial screening visit)
- Negative voiding cytology for high-grade disease within 8 weeks before screening
Key exclusion criteria are as follows:
- Received BCG treatment for urothelial carcinoma within the previous 1 year
- History of high-grade bladder cancer (papillary or CIS) in the past 2 years
- Past or current muscle invasive disease or metastatic urothelial carcinoma
- Concurrent tumor grading of T1
- Concurrent upper tract urothelial carcinoma
- History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous TURBT
Response will be assessed by cystoscopy, histopathology (if applicable), and urine cytology every 3 months (every 6 months after 2 years).
Non-complete response patients at 3 months will undergo standard of care treatment and then enter follow-up. Patients with disease recurrence or progression during follow-up will undergo standard of care treatment and then end-of-study procedures 3 months later.
The primary objective of this study is to evaluate the tumor ablative effect of UGN-102 in patients with low grade non-muscle invasive bladder cancer. The secondary objectives include the evaluation of durability of response and to evaluate the safety and tolerability of intravesical instillations of UGN-102 in patients with low-grade non-muscle invasive bladder cancer. The primary endpoint is complete response rate at 3 months after the start of treatment. Secondary endpoints include:
- Duration of response (key secondary)
- Durable complete response rate at scheduled disease assessment time points
- Disease-free survival
- Safety/tolerability
Point estimates of complete response and durable complete response rates with exact 95% confidence intervals will be summarized. Duration of response and disease-free survival will be estimated using the Kaplan Meier method.
This study is currently recruiting (NCT05243550).
Presented by: Christine E. Lentowski, MS, MBS, UroGen® Pharma, Princeton, New Jersey
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 23rd Annual Meeting of the Society of Urologic Oncology (SUO), Nov 30 – Dec 2, 2022. San Diego, CA
References:
- Chevli KK, Shore ND, Trainer A, et al. Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A phase 2b, open-label, single-arm trial. J Urol. 2022 Jan;207(1):61-69.