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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
Source:
Title:

Irreversible inhibition of HER2 activating mutations with neratinib enhances the pre-clinical efficacy of trastuzumab emtansine and trastuzumab deruxtecan

Published date:
11/17/2020
Excerpt:
WHIM51 has HER2 exon 20 insertion mutation at amino acid 776 (ERBB2 A775_G776insYVMA) and WHIM64 has a HER2 L869R missense mutation....We have tested both the combinations of neratinib + T-DXd and neratinib + T-DM1 in vivo in both HER2 mutant PDX’s and observed statistically significant tumor regression with the neratinib + ADC combinations as compared to either T-DXd or T-DM1 on its own....Neratinib increases the endocytosis of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), thereby increasing tumor cell kill and causing greater tumor regression in HER2 mutated MBC.