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.

BRAF Dimer Inhibitor V600 and BRAF Class 2/3

Geo Regions

BRAF Dimer Inhibitor V600 and BRAF Class 2/3

PF-07799933, ARRY-440 is an investigational compound. Its safety and efficacy have not been established.

Overview + Rationale

  • PF-07799933 is a selective ATP-competitive small-molecule RAF kinase inhibitor, which has been shown to suppress the RAF/MEK/ERK pathway in tumor cells expressing BRAF V600-mutant (Class I) and non-V600-altered (Class II and III) kinase
  • In various xenograft models, PF-07799933 has shown anti-tumor activity alone and in combination with clinically relevant targeted therapeutics and drug exposure in the brain

Mechanism of Action

  • PF-07799933 binds to and inhibits BRAF Class I mutants (activated, monomeric V600 mutations), BRAF Class II mutants (activated, dimeric mutations), and BRAF Class III mutants (loss-of-function mutations that transactivate wildtype BRAF heterodimers) and has the potential to treat tumors with these de novo and acquired mutations in the BRAF gene. 
  • PF-07799933 is also highly brain-penetrant, which could address primary or metastatic CNS disease.
  • PF-07799933 is highly selective for inhibition of only BRAF, which provides a wide therapeutic safety index that allows for maximal target coverage and tolerability

Stage of Development

small icon representing early solid tumors
Advanced Solid Tumors
Phase 1 Monotherapy and Combination