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 alpha-V/beta-8 Antagonist

Geo Regions

Integrin alpha-V/beta-8 Antagonist

PF-06940434 is an investigational compound. Its safety and efficacy have not been established.

Overview + Rationale

  • Integrins are cell-surface adhesion molecules that mediate cell–cell, cell–extracellular matrix, and cell–pathogen interactions. In mammals, 24 different integrins are formed by specific, noncovalent association of 18 α-subunits with 8 β-subunits
  • Integrins αVβ6 and αVβ8 are specialized for binding to and releasing TGF-β from its surrounding LAP prodomain, thereby activating it 
  • In many solid tumors, the immunosuppressive TGF-β pathway is associated with poor prognosis. TGF-β is thought to promote tumor development via proliferation, immune cell exclusion and inhibition of function and suppressive immune cell differentiation 
  • Recent studies suggest that increased TGF-β activity in tumor stroma is thought to prevent tumor penetration by cytotoxic CD8+ T cells and may prevent response to PD-L1 inhibitors 
  • Integrin αvβ8–expressing tumor cells thus evade host immunity by regulating TGF-β activation in immune cells and could be a potential oncology target 
  • PF-06940434 is an antagonist of integrin alpha-V/beta-8 (αvβ8)

Mechanism of Action

By blocking integrin aVβ8, in preclinical studies, PF-06940434 inhibited the release of active TGFβ1 & 3 into the tumor microenvironment

Stage of Development

small icon image other cancer
Advanced or Metastatic Solid Tumors
Phase 1 Monotherapy and Combination*

*Closed to Enrollment

REFERENCES: Wang J et al. Atypical features of integrin αVβ8. Proc Natl Acad Sci U S A. 2017;114(21):E4168-E4174. Takasaka N et al. Integrin αvβ8–expressing tumor cells evade host immunity by regulating TGF-β activation in immune cells. JCI Insight. 2018;3(20):e122591. NCI Thesaurus. https://thesaurus.cancer.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&version=20.10d&code=C172097&ns=ncit Accessed May 18, 2023; ClinicalTrials.gov. Accessed October 30, 2023. http://clinicaltrials.gov/