423RO Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): Updated efficacy analysis from the HER2CLIMB-02 trial

In Part A, ORR (39% vs 25%), median PFS (7 vs 3 months) and PFS-6 (50% vs 40%) suggested preliminary evidence of efficacy among pts with HR+/HER2-MBC vs TNBC.No differences in efficacy between tumor types were seen in Part B. Ninety nine percent of pts experienced a tx-emergent adverse event (TEAE; Grade 3: A 52%, B: 48%, Z: 57%).Common TEAEs included nausea (52%), fatigue (41%), diarrhea (35%), vomiting (31%), neutrophil count decreased (27%), anemia (26%), and hypokalemia (26%).Five pts (4%) had tx-related interstitial lung disease (ILD) by adjudication, 2 of whom died. Conclusions:Efficacy in Part A (ADC nave) was clinically meaningful, supporting development of HER3-DXd in earlier-line settings.In contrast, limited activity was observed in Parts B and Z (tx w/ prior ADC with topoisomerase I payload) with HER3-DXd monotherapy.No cumulative toxicity was observed, and overall safety findings were consistent with previous studies.Efficacy according to HER3 expression will be presented in future publications.