189O A phase II study of patritumab deruxtecan (HER3-DXd), in patients (pts) with advanced breast cancer (ABC), with biomarker analysis to characterize response to therapy (ICARUS-BREAST01)

Abstract

HER3 plays a key oncogenic role in breast cancer, being associated with poor prognosis and resistance to PI3K/AKT/mTOR inhibitors (inh) and endocrine therapy (ET). HER3-DXd is an anti-HER3 monoclonal antibody conjugated to a topoisomerase I inh by a peptide-based cleavable linker, which showed activity in HER3-expressing ABC (NCT02980341). ICARUS-BREAST01 (NCT04965766) is an ongoing multi-center, single-arm, phase II study in pts with HR+ and HER2- ABC, unselected for HER3 expression, who progressed on CDK 4/6 inh, any line of targeted/ET and 1 line of chemotherapy for ABC. Enrolled pts receive HER3-DXd 5.6 mg/kg IV every 3 weeks and undergo tumor biopsy at baseline, on-treatment and end of treatment (EoT); 100 pts are planned; enrollment on HER3 IHC expression level was removed by amendment on Apr 21st, 2022. Primary endpoint is confirmed objective response rate; secondary: progression-free survival; duration of response; clinical benefit rate; overall survival and safety. We report the 3-months response rate (3m-RR) of patients included before Sept 15 2022 and safety data up to Nov 4 2022, based on data cut-off [DCO] of Jan 23, 2023. Multiplex imaging mass cytometry, DNA sequencing, circulating tumor cells (CTC) and association with treatment response will be presented. At DCO, 85 pts were included in the study and 56 were evaluable for this analysis. Pts and treatment characteristics are reported in the table. Among the 56 pts: 16 had partial response, 30 stable disease, 10 progressive disease. The 3 m-RR was 28.6% [95%CI: 18.4-41.5]. Most common any-grade adverse events (AEs) were: fatigue (89.3%), nausea (76.8%); most frequent grade ≥3 AEs was fatigue (14.0%). Confirmed ILD: 1 G1 (1.8%). Table: 189OCharacteristicsPatients N = 56 [range]; (%)Median age, years57 [28; 82]Median lines of therapy for ABC4 [2; 8]Median HER3-DXd cycles7 [3;20]Treatment discontinuationDisease progressionAdverse events (AEs)Others32 (57.1%)2363 Open table in a new tab HER3-DXd showed early signs of activity and a manageable safety profile in pts with HR+ HER2- ABC. Results on biomarkers analysis will also be presented.