Abstract 1672: Enhanced delivery and activity of a novel antibody-drug conjugate, PF-08052667, for treatment of non-muscle invasive bladder cancer

Abstract PF-08052667 is a novel antibody-drug conjugate (ADC) under investigation for intravesical treatment of non-muscle invasive bladder cancer (NMIBC). Intravesical administration remains the standard approach patients with high-risk NMIBC. While this route allows direct access to the bladder lumen and tumor cells, drugs such as Bacillus Calmette-Guérin (BCG) and other chemotherapies are typically retained for less than two hours and evacuated after instillation. Current BCG supply issues, along with a documented lack of sustained response in about two-thirds of cases, highlight the demand for alternative treatment options such as ADCs which have proven activity in bladder cancer. PF-08052667 is an integrin beta-6 (IB6)-directed MMAE ADC specifically designed for intravesical treatment of NMIBC with eight MMAE molecules per ADC via a pegylated glucuronide linker. Prior to ADC administration, a bladder prewash is performed to increase urothelial permeability, enhance drug uptake into bladder tissue, and improve antitumor activity while maintaining low systemic exposure and a favorable safety profile. Here, we present the optimization of PF-08052667 for local delivery through ADC design and incorporation of a n-dodecyl-β-D-maltoside (DDM)-containing bladder prewash. In vitro and in vivo studies assessed tissue retention, tissue penetration, and antitumor efficacy with PF-08052667 or a rodent-specific surrogate ADC administered alone or following a bladder prewash. Additionally, tolerability and systemic exposures were evaluated in pharmacologically relevant animal models. High IB6 expression was confirmed across a panel of NMIBC tumors. In vitro, PF-08052667 demonstrated robust cytotoxic activity in a variety of IB6-expressing bladder cancer cell lines and NMIBC patient-derived organoids. The combination of PF-08052667 with bladder prewash resulted in up to 42-fold higher bladder tissue MMAE concentrations, improved tissue penetration and residence time, and achieved significant tumor control in orthotopic NMIBC mouse models. Following repeated local administration of PF-08052667 with bladder prewash, systemic exposure remained minimal, and no systemic toxicity was detected. Overall, these findings support the clinical development of PF-08052667 with bladder prewash, which is being evaluated for safety and antitumor efficacy in a Phase I trial (NCT07206225) involving patients with NMIBC. Citation Format: Christopher M. Carosino, Devra Olson, David Ortiz, Steven Duniho, Maddy Burcher, Eliana Moskovitz, Rebecca Mazahreh, Iliyana Mikell, Matthew R. Levengood, Sharsti Sandall, Joeseph D. Dekker, . Enhanced delivery and activity of a novel antibody-drug conjugate, PF-08052667, for treatment of non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1672.