340O - Efficacy, safety and biomarker analysis of ICARUS-BREAST01: A phase II study of patritumab deruxtecan (HER3-DXd) in patients (pts) with HR+/HER2- advanced breast cancer (ABC)

Background

Despite the improved clinical outcomes achieved with endocrine therapy (ET) + CDK4/6 inhibitors (inh) in HR+/HER2- ABC, few effective therapeutic agents are available beyond progression. Human Epidermal Growth Factor Receptor-3 (HER3) expression is associated with poor prognosis and resistance to PI3K/AKT/mTOR inh and ET. HER3-DXd is an antibody drug conjugate composed of an anti-HER3 monoclonal antibody conjugated to a topoisomerase-I inh by a cleavable peptide linker. ICARUS-BREAST01 (NCT04965766) is an academic, multi-center, single-arm, phase 2 study evaluating activity, safety and biomarkers of response/resistance to HER3-DXd in pts with HR+/HER2- ABC, who progressed on CDK 4/6 inh and one line of chemotherapy.

Methods

Adult pts were enrolled to receive HER3-DXd 5.6 mg/kg IV every 3 weeks until progression or unacceptable toxicity. Primary endpoint: confirmed objective response rate (cORR) by local investigator assessment. Secondary endpoints: clinical benefit rate (CBR), progression-free survival (PFS), duration of response (DOR), safety. Exploratory translational analyses were conducted on blood and tumor samples.

Results

At Apr 16^th 2024 data cutoff, 99 pts were included and 19 are still on treatment. Median age was 57.0 years [IQR 48.0;66.0], median (m) duration of prior CDK4/6inh 13.7 months (mos) [IQR 6.5;19.7]. At a mfollow-up of 15.3 mos [95%CI 13.0;17.2], cORR was 53.5% [95%CI 43.2; 63.6], CBR 63.6% [95%CI 53.4;73.1]; mPFS 9.4 mos [95%CI 8.1;13.4]; mDOR 8.7 mos [95%CI 8.1;12.5]. Adverse events (AEs; any grade/≥3) occurred in 98.0%/ 55.6% of pts. AEs led to dose reduction/discontinuation in 20.2%/12.1%. The most frequent treatment-related AEs were nausea (75%; G3 5%), diarrhea (53%; G3 1%), 6 pts had centrally adjudicated interstitial lung disease (5 G1, 1 G2). Data on HER3 expression and translational analyses on tumor and blood samples will be presented.

Conclusions

HER3-DXd showed clinically meaningful activity and manageable safety profile in patients with HR+/HER2- ABC progressing after 2 or more lines of therapy. Further studies are warranted to confirm the role of HER3-DXd in this setting.

Clinical trial identification

NCT04965766.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy Cancer Centre.

Funding

Daiichi Sankyo.

Disclosure

B. Pistilli: Financial Interests, Institutional, Advisory Board: Astrazeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: Astrazeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Steering Committee Member: Astrazeneca, Novartis; Financial Interests, Institutional, Research Grant: Astrazeneca; Financial Interests, Institutional, Local PI: Astrazeneca, Gilead, Seagen, MSD, Novartis; 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, Eisai; Financial Interests, Institutional, Advisory Board: Exactscience, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Coordinating PI: AstraZeneca, Seagen; Financial Interests, Local PI: MSD, Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Novartis, lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD. F. Dalenc: Financial Interests, Institutional, Advisory Board: Novartis, MSD, Daiichi Sankyo, Astrazeneca; Financial Interests, Institutional, Steering Committee Member: Astrazeneca; Non-Financial Interests, Principal Investigator: Roche, gilead, Novartis; Non-Financial Interests, Advisory Role: AstraZeneca. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. D. Loirat: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Pfizer, Novartis, ExactSciences; Financial Interests, Personal, Other, Travel/congress: MSD; Financial Interests, Personal, Other, Travel/Congress: Roche, AstraZeneca, Gilead, Novartis; Financial Interests, Personal, Invited Speaker: Gilead, Lilly; Financial Interests, Personal, Other, Travel/Congres: Pflizer. A. Sporchia: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. F. Suto: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, Owkin. All other authors have declared no conflicts of interest.