Pharmacokinetics of UGN‑102, an investigational mitomycin‑containing reverse thermal gel for the treatment of non-muscle invasive bladder cancer.

PURPOSE: To evaluate the pharmacokinetic properties of UGN-102, a mitomycin-containing reverse thermal gel. METHODS: Twelve patients with NMIBC received 6 once-weekly intravesical instillations of UGN-102 (BL004: 120 mg mitomycin [n = 6]; BL005: 75 mg mitomycin [n = 6]). Plasma samples for determination of pharmacokinetic (PK) parameters were collected up to 6 h following instillation. RESULTS: In BL004, mean Cmax was 20.39 ng/mL, and median was 16.10 ng/mL (range 4.00-40.40), 100-10-fold lower than reported myelosuppression toxic level (RMTL); and median Tmax was 1.5 h. Mean AUC0-6 was 56.23 ng·h/mL and mean apparent terminal half-life (t1/2) was 49 min. The highest observed Cmax (40.40 ng/mL) was 59-fold and 13-fold lower than Cmax following IV 30 mg or 10 mg mitomycin, respectively, and 10-fold lower than the RMTL. Maximum measured urine concentration was 635 µg/mL. In BL005, mean Cmax was 2.27 ng/mL, 181-fold lower than the RMTL; mean Tmax was 1.95 h and mean AUC0-6 was 5.69 ng·h/mL. At 4-6 h post intravesical instillation, mitomycin concentrations in urine were either below or approaching the lower level of quantification (< 0.250 µg/mL) in 5/6 patients. In the remaining patient, the measurable urine concentrations over the 6-hour period suggest dwell time was > 6 h post-instillation, possibly due to the tumor location restricting urine flow. However systemic exposure was < 4 ng/mL, 100-fold lower than the RMTL. CONCLUSIONS: Intravesical instillation of UGN-102 results in low-level systemic absorption of mitomycin, with Cmax values considerably lower than those following IV administration and those associated with myelosuppression. STUDY REGISTRATION: BL004: NCT02307487; BL005: NCT03558503.