189O - A phase 2 Study of Patritumab Deruxtecan (HER3-DXd), in patients (pts) with advanced breast cancer (ABC), with biomarker analysis to characterize response to therapy (ICARUS-BREAST01)

Background

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.

Methods

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 21^st, 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.

Results

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: 189O

Conclusions

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.

Clinical trial identification

NCT04965766.

Legal entity responsible for the study

Gustave Roussy.

Funding

Daiichi Sankyo.

Disclosure

B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen; Financial Interests, Institutional, Advisory Board: Exact science, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Invited Speaker: AstraZeneca, Seagen, MSD, Daiichi; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi, MSD. F. Dalenc: Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Gilead, Novartis. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca. M. Benderra: Financial Interests, Invited Speaker: Novartis, Lilly, AstraZeneca, MSD, GSK, Gilead; Financial Interests, Other: Pfizer, Novartis, Lilly, AstraZeneca. D. Sellami: Financial Interests, Full or part-time Employment: Daiichi Sankyo S. Michiels: Financial Interests, Personal, Other, Statistical advice: Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan, IQVIA, Kedrion. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: MedImmune, Gilead, Relay Therapeutics; Other, Founder: Pegacsy. All other authors have declared no conflicts of interest.