PF-06940434 Advanced Drug Monograph

PF-06940434

English Name: PF-06940434

Mechanism of Action: PF-06940434 is an investigational antagonist of integrin $\alpha$V$\beta$8. Integrins are cell surface adhesion molecules. $\alpha$V$\beta$8 is involved in binding to and releasing transforming growth factor-beta (TGF-$\beta$) from its latent form, thereby activating it. The TGF-$\beta$ pathway is immunosuppressive and associated with poor prognosis in many solid tumors, promoting tumor development through various mechanisms including immune cell exclusion. By blocking $\alpha$V$\beta$8, PF-06940434 aims to inhibit the release of active TGF-$\beta$ in the tumor microenvironment, thereby abrogating TGF-$\beta$-mediated immunosuppression, enhancing anti-tumor immunity, and potentially leading to tumor cell death and reduced cancer cell proliferation.

Status: Investigational compound. Safety and efficacy not established.

Development Phase: Phase 1

Clinical Trials: Currently or has been in Phase 1 clinical trials for advanced or metastatic solid tumors. A study (NCT04152018) evaluated the safety, pharmacokinetics, and pharmacodynamics of escalating doses of PF-06940434 as a single agent and in combination with an anti-PD-1 agent (sasanlimab/PF-06801591). This study included patients with various solid tumors such as squamous cell carcinoma of the head and neck (SCCHN), renal cell carcinoma (RCC), ovarian, gastric, esophageal, lung squamous cell, pancreatic, biliary duct, endometrial, melanoma, and urothelial cancer. The trial has been terminated based on strategic considerations and not due to specific safety reasons or a request from a regulatory authority.

Potential Uses (Investigational): Treatment of advanced or metastatic solid tumors, including but not limited to SCCHN, RCC, ovarian cancer, gastric cancer, esophageal cancer, lung squamous cell carcinoma, pancreatic cancer, bile duct cancer, endometrial cancer, melanoma, and urothelial cancer, potentially in combination with other anti-cancer therapies.

Side Effects: As an investigational agent, the full profile of potential side effects is still under investigation. Information regarding specific adverse events would be found in the results of the clinical trials.