SHP2 is a protein-tyrosine phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/MAPK pathway to regulate cellular proliferation and survival. Overactivity of SHP2 is a critical contributor to many forms of cancer, is a mechanism of resistance to several targeted therapies, and can suppress antitumor immunity.

EGFR mutations occur in approximately 40-50% of NSCLC cases in Asia, more than twice the rate observed in the United States. By combining SHP2 inhibition and EGFR inhibition, there is potential to prevent oncogenesis and overactive cellular proliferation.

"BBP-398 is a potential best-in-class SHP2 inhibitor that was designed to maximize combination potential,” said Yizhe Wang, Ph.D., Chief Executive Officer of LianBio. “EGFR-mutant non-small cell lung cancer patients who develop resistance to osimertinib currently have limited treatment options, and we look forward to evaluating BBP-398’s ability to restore sensitivity to osimertinib when used as a combination agent.”

The multi-center, open-label Phase 1 trial is designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of BBP-398 in combination with osimertinib in patients with locally advanced or metastatic NSCLC with EGFR mutations. The trial includes a dose escalation phase, followed by expansion cohorts. In July 2023, LianBio announced a clinical supply agreement with AstraZeneca in China to procure osimertinib for this trial.