EP08.02-049 A Phase I Trial of the HER2 Exon 20 Inhibitor, BI 1810631, In Patients With Advanced Solid Tumors With HER2 Aberrations

Abstract

HER2 mutations are present in 2-4% of NSCLC tumors; of these ∼50% are exon 20 insertion (ex20ins) mutations. There is an unmet need for effective targeted therapy against HER2 mutations in solid tumors, particularly in NSCLC. Historically, ex20ins mutations have responded poorly to TKIs. Moreover, TKIs that inhibit both mutant EGFR and HER2 are typically limited by toxicities associated with inhibition of wild-type EGFR. Despite the promise of trastuzumab deruxtecan and other agents in this setting, the development of orally available selective TKIs is important given the heterogeneity of HER2 aberrations, potential for combination regimens, and the risk of interstitial lung disease with ADCs.