TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss
Status:
Active, not recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
The PI3K, protein kinase B (AKT), and mTOR signaling network promotes cell growth, survival,
metabolism, and motility, but becomes a critical oncogenic driver under aberrant conditions
that control the tumor microenvironment and angiogenesis. The PI3K-AKT-mTOR axis is the most
frequently deregulated signaling pathway in primary osteosarcoma and other bone tumors. PI3Ka
has high rates of 25-50% activating mutations associated with tumor formation in
osteosarcoma. Other causes of pathway hyperactivation include loss of function of the tumor
suppressor PTEN, gain-of-function mutations in AKT and PDK1, or upregulation of receptor
tyrosine kinases. TQB3525 is an orally bioavailable, potent, dual catalytic site inhibitor of
PI3Ka and PI3Kd. Tumor growth inhibition has been demonstrated in multiple xenograft
osteosarcoma models with PI3K-mutant, PTEN-null cell lines. The investigators try to
investigate TQB3525 in primary osteosarcoma and other bone tumors for its safety,
tolerability, dose-limiting toxicities (DLT), MTD and antitumor efficacy.