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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Integrin Beta-6 (IB6) Directed Top1 Inhibitor

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Integrin Beta-6 (IB6) Directed Top1 Inhibitor

PF-08046876 | B6C is an investigational compound. Its safety and efficacy have not been established.

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Overview + Rationale

Rationale for Cancer Target

  • IB6 is a cell surface receptor involved in cell–extracellular matrix interactions and has been implicated in solid tumor pathogenesis and invasiveness1,2
  • IB6 expression is normally low in nonmalignant tissue (gastrointestinal tract, hair follicles, lung, renal tubules) but is reported to be increased in certain pathological contexts, including tumor development3-5
  • IB6 expression has been detected in multiple solid tumor types including pancreatic ductal adenocarcinoma 6-10
  • Elevated IB6 has been associated with poor clinical outcomes 9

 

Overview

PF-08046876 (B6C) is an investigational antibody-drug conjugate (ADC) composed of an anti-IB6 antibody conjugated to a camptothecin-class topoisomerase I (TOP1) inhibitor, AMDCPT, using a traceless enzyme-cleavable glucuronide linker11

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.1
  • In preclinical studies, B6C has shown potency, bystander effect, and reduced susceptibility to efflux pumps1

 

 

Stage of Development

Other

Advanced Solid Tumors

Phase 1 Monotherapy
This information is current as of May 5th 2026.

TOP1 =Topoisomerase 1

REFERENCES:. 1. Harisi R. Onco Targets Ther. 2015;8:1387-1398. 2. Niu J. Cancer Lett. 2017;403:128-137. 3. Desgrosellier JS. Nat Rev Cancer. 2010;10:9-22. 4. Bandyopadhyay A. Curr Drug Targets. 2009;10:645-652. 5. Brzozowska E and Deshmukh S. Int J Mol Sci. 2022;23:12346. 6. Lyon RP. Mol Cancer Ther. 2023;22:1444-1453. 7. Koopman Van Aarsen LA. Cancer Res. 2008;68:561-570. 8. Li F. Canc Manag Res. 2020;12:9599-9608. 9. Elayadi AN. Cancer Res. 2007;67:5889-5895; 10. Zhong C. Arch Med Sci. 2021 Mar 26:20(1):267-279; 11. Mazahreh, R et al. Cancer Res 2025;85(8_Suppl_1): Abstract nr 1577; 12.NCT07090499. https://clinicaltrials.gov/study/NCT07090499 Accessed April 16, 2026.