Abstract 339TiP
Background
Pre-clinical evidence and retrospective studies suggest that PAM50 HER2-Enriched (HER2-E), hormone receptor-positive (HR+)/HER2-negative tumors have estrogen receptor (ER)-independency and poor prognosis but seem to have androgen receptor (AR)-addiction. Enzalutamide (EZM) is a potent inhibitor of androgen receptor signaling. AR expression has been shown to induce resistance to both tamoxifen and aromatase inhibitors in estrogen receptor HR–expressing cell lines. The trial hypothesizes that EZM induces a significant proliferative arrest in PAM50 HER2-E, HR+/HER2-negative advanced breast cancer (BC), leading to clinical benefit in this poor prognosis population.
Trial design
SOLTI-1502 ARIANNA is an exploratory, phase II trial with two independent cohorts evaluating the effect of EZM on proliferation after 2 weeks (+7 days window) of treatment in pre- or post-menopausal female or male patients with endocrine-resistant, locally advanced, or metastatic HR+/HER2-negative BC. Cohort A will include patients with PAM50 HER2-E tumors and Cohort B patients with PAM50 Luminal A/B tumors. Fresh tumor biopsy will be obtained at screening and sent to central laboratory for PAM50 subtyping determination. Patients will receive EZM 160 mg once a day. Following 2 weeks of treatment, a tumor biopsy from the same baseline lesion will be obtained. Tumor assessment will be performed every 8 weeks during first year. Treatment will continue until disease progression. The primary objective is to evaluate the anti-proliferative effect of EZM after 2 weeks, measured as relative changes in the PAM50 11-gene proliferation-related signature by the PAM50 nCounter-based assay in Cohort A. Secondary objectives include: anti-proliferative effect of EZM after 2 weeks of treatment in Cohort B, overall response rate, progression-free survival, safety and further correlative molecular analyses. The trial is active in 8 sites, enrolling patients since July 2020. Previous TIP was presented in SABCS2020.
Clinical trial identification
Trial identification: NCT04142060.
Editorial acknowledgement
Legal entity responsible for the study
SOLTI innovative cancer research.
Funding
Funding was granted by the Breast Cancer Research Foundation (ARP-18-003) and drug was supplied by Astellas, Inc.
Disclosure
L. Manso: Financial Interests, Personal, Advisory Role, travel and accommodation paid: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role, travel and accommodation paid: Novartis; Financial Interests, Personal, Advisory Role, travel and accommodation paid: Tesaro; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Tesaro; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Research Grant: Tesaro. S. Pernas: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Polyphor; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role, travel and accommodation paid: Novartis; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Pierre-Fabre. X. González: Financial Interests, Personal, Advisory Role: Solti Breast Cancer Group; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Eisai. C.M. Perou: Financial Interests, Personal, Stocks/Shares: BioClassifier LLC; Financial Interests, Personal, Advisory Role: BioClassifier; Financial Interests, Personal, Ownership Interest: Breast PAM50; Financial Interests, Personal, Royalties: Breast PAM50. A. Prat: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Other, travel, accommodations and expenses paid: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Nanostring Technologies; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Oncolytics Biotech; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: PUMA; Financial Interests, Personal, Advisory Role: Daiichi Sankyo. M. Oliveira: Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: PUMA Biotechnology; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pierre-Fabre; Financial Interests, Personal, Advisory Role: GP Pharma; Financial Interests, Personal, Advisory Role: Grünenthal; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Philips Healthcare; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Immunomedics; Financial Interests, Personal, Research Grant: Seattle Genetics; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: PUMA Biotechnology; Financial Interests, Personal, Research Grant: Zenith Epigenetics; Financial Interests, Personal, Other, travel and accommodation paid: Novartis; Financial Interests, Personal, Other, travel and accommodation paid: ROCHE; Financial Interests, Personal, Other, travel and accommodation paid: Pierre Fabre; Financial Interests, Personal, Other, travel and accommodation paid: GP Pharma; Financial Interests, Personal, Other, travel and accommodation paid: Grünenthal; Financial Interests, Personal, Other, travel and accommodation paid: Eisai. All other authors have declared no conflicts of interest.