Randomized phase II trial of venetoclax + fulvestrant versus fulvestrant in estrogen receptor+, HER2– locally advanced or metastatic breast cancer following recurrence or progression during or after a CDK4/6 inhibitor: VERONICA.

Authors

null

Geoffrey J Lindeman

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

Geoffrey J Lindeman , Aditya Bardia , Rebecca Bowen , Aulde Flechais , Guiyuan Lei , Alexandra Hogea , Mehrdad Mobasher , Saeed Rafii

Organizations

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Department of Oncology, Royal United Hospitals Bath NHS Foundation Trust, Bath, United Kingdom, Global Pharma Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Roche Products Ltd, Welwyn Garden City, United Kingdom, Product Development Oncology, Genentech Inc, South San Francisco, CA

Research Funding

Pharmaceutical/Biotech Company

Background: CDK4/6 inhibitors (CDK4/6is) administered with endocrine therapy have demonstrated improvements in progression-free survival (PFS) for estrogen receptor (ER)+ advanced breast cancer (BC), but resistance occurs, and new options are needed in the post-CDK4/6i setting. BCL2 is an estrogen-responsive anti-apoptotic molecule overexpressed in 75% of BCs. The BCL2 inhibitor venetoclax (Ven) has shown improved outcomes and tolerability in hematological malignancies such as chronic lymphocytic leukemia, and has been investigated in BC. A phase 1b study of Ven + tamoxifen demonstrated safety and an efficacy signal in ER+, BCL2+ metastatic BC (mBC). Preclinical data for Ven + fulvestrant (Ful) have also shown synergy. Based on these proof-of-principle data, the current study evaluates safety and efficacy of Ven + Ful vs Ful in women with ER+, HER2– locally advanced (LA)/mBC progressing after first- or second-line of prior therapy for metastatic disease, including ≥8 wks of a CDK4/6i. Methods: VERONICA is a global, randomized, phase 2, multicenter, open-label study. Eligible patients (pts) are aged ≥18 yrs with confirmed ER+, HER2–, inoperable LA/mBC, ≥1 measurable lesion, tissue evaluable for BCL2, and ECOG performance status 0–1. Prior Ful or Ven, or prior chemotherapy for LA/mBC are prohibited. Stratified by BCL2 expression (low vs high) and number of prior lines of mBC therapy (1 vs 2), pts are randomized 1:1 to Ven 800 mg PO daily + Ful 500 mg IM (cycle 1 days 1 and 15, and day 1 of each subsequent 28-day cycle) vs Ful 500 mg IM alone. Treatment continues until disease progression or intolerable toxicity. Primary endpoint is clinical benefit rate defined as complete/partial response + stable disease for ≥24 wks from randomization. Secondary efficacy endpoints include PFS, objective response rate, duration of response, and overall survival. Safety, pharmacokinetic, biomarker (e.g. BCL2 and PI3K expression) and patient-reported outcome analyses will also be conducted. Currently, 21 of the planned 100 pts have been enrolled; enrollment is ongoing. Clinical trial information: NCT03584009

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Hormone Receptor-Positive

Clinical Trial Registration Number

NCT03584009

Citation

J Clin Oncol 37, 2019 (suppl; abstr TPS1108)

DOI

10.1200/JCO.2019.37.15_suppl.TPS1108

Abstract #

TPS1108

Poster Bd #

185a

Abstract Disclosures