Enhanced delivery and activity of a novel antibody-drug conjugate, PF-08052667, for treatment of non-muscle invasive bladder cancer
Presenter: Chris Carosino, BS;PhD Session: Antibody-Drug Conjugates and Linker Engineering 1 Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
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 Pfizer, Inc., Bothell, WA
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.
Disclosure
C. M. Carosino, Pfizer Employment, Stock, Stock Option. D. Olson, Pfizer Employment, Stock, Stock Option. D. Ortiz, Pfizer Employment, Stock, Stock Option. S. Duniho, Pfizer Employment, Stock, Stock Option. M. Burcher, PFizer Employment, Stock, Stock Option. E. Moskovitz, Pfizer Employment, Stock, Stock Option. R. Mazahreh, Pfizer Employment, Stock, Stock Option. I. Mikell, Pfizer Employment, Stock, Stock Option. M. R. Levengood, Pfizer Employment, Stock, Stock Option. S. Sandall, Pfizer Employment, Stock, Stock Option. J. D. Dekker, Pfizer Employment, Stock, Stock Option.
Cited in
Control: 4344 · Presentation Id: 5344 · Meeting 21436