BackIntegrin Beta-6 (Iβ6) Directed Top1 Inhibitor
PF-08046876 | B6C is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
Rationale for Cancer Target
- Iβ6 is a cell surface receptor that promotes cellular adhesion through interactions with the extracellular matrix, which plays a major role in solid tumor pathogenesis and invasiveness1,2
- Iβ6 expression is normally low in nonmalignant tissue (Gastrointestinal tract, hair follicles, lung, renal tubules) but is highly upregulated during tumor pathogenesis3-5
- Iβ6 is expressed in numerous solid tumors including non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal cancer, bladder cancer and cutaneous squamous cell carcinoma6-9, 11
- Iβ6 is a proposed negative prognostic marker based on multiple analyses9-10
Overview
PF-08046876 | B6C is an investigational antibody-drug conjugate (ADC) composed of an anti-IB6 antibody conjugated to a camptothecin-class topoisomerase I (TOPO1) inhibitor, AMDCPT, using a traceless enzyme-cleavable glucuronide linker.11
Mechanism of Action
- PF-08046876 has demonstrated activity in vitro and in multiple in vivo models
- Targeted delivery of AMDCPT to IB6-expressing tumor cells is the primary hypothesized mechanism of action of B6C. The direct cytotoxicity may be complemented by secondary effects, including bystander effect.11
- In preclinical studies, B6C has shown potency, bystander effect, and susceptibility to efflux pumps11
Stage of Development
Advanced Solid Tumors
Phase 1 Monotherapy