Abstract
evERA Breast Cancer (BC): Phase III study of giredestrant + everolimus vs exemestane + everolimus in patients (pts) with estrogen receptor-positive, HER2-negative locally advanced or metastatic BC (ER+, HER2– LA/mBC).
Author
Erica L. Mayer
Dana-Farber Cancer Institute, Boston, MA
info_outline
Erica L. Mayer, Sara M. Tolaney, Adam Brufsky, William John Gradishar, Komal L. Jhaveri, Miguel Martin, Luca Moscetti, Andreas Schneeweiss, Gregory A. Vidal, Patricia Cortazar, Merilin Feldman, Bann-mo Day, Hope S. Rugo
Full text
Authors
Erica L. Mayer
Dana-Farber Cancer Institute, Boston, MA
info_outline
Erica L. Mayer, Sara M. Tolaney, Adam Brufsky, William John Gradishar, Komal L. Jhaveri, Miguel Martin, Luca Moscetti, Andreas Schneeweiss, Gregory A. Vidal, Patricia Cortazar, Merilin Feldman, Bann-mo Day, Hope S. Rugo
Organizations
Dana-Farber Cancer Institute, Boston, MA, UPMC Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, Memorial Sloan Kettering Cancer Center, New York, NY, Hospital Gregorio Maranon, Universidad Complutense, GEICAM, CIBERONC, Madrid, Spain, Universitaria Policlinico Modena, Modena, Italy, National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, The West Cancer Center, Germantown, TN, Genentech, Inc., South San Francisco, CA, University of San Francisco, San Francisco, CA
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
F. Hoffmann-La Roche Ltd
Background:
Endocrine therapy (ET) + a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is the standard of care in pts with ER+, HER2– mBC in the first-line setting. Fulvestrant ± a CDK4/6i, and everolimus + exemestane are the current approved second-line regimens. However, therapeutic resistance to some ETs, such as aromatase inhibitors, can arise from
ESR1
mutations (m) driving estrogen-independent transcription and proliferation. Current post-CDK4/6i treatment options are suboptimal. New therapy options are therefore needed to reduce this risk and to improve outcomes, tolerability, quality of life, and adherence to treatment. Giredestrant is a highly potent, nonsteroidal oral selective ER antagonist and degrader (SERD) that achieves robust ER occupancy and is active regardless of
ESR1
-mut status. While Phase I SERD combination data in the post-CDK4/6i setting are encouraging, there are no randomized combination data. Combining giredestrant and everolimus may improve outcomes after CDK4/6is and in pts with
ESR1
m tumors.
Methods:
evERA BC (NCT05306340), a Phase III, global, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant + everolimus vs. exemestane + everolimus in pts with ER+, HER2– LA/mBC who had previous treatment with a CDK4/6i and ET in the LA/mBC or adjuvant setting. Pts will be randomized to either giredestrant (30 mg) + everolimus (10 mg) by mouth (PO) every day (QD), or exemestane (25 mg) + everolimus (10 mg) PO QD. Pts will receive treatment until disease progression or unacceptable toxicity. Pts will use a dexamethasone mouth rinse 4 times QD for 8 weeks concurrently with study treatment. Eligibility: Female/male pts ≥ 18 years with ER+, HER2– LA/mBC and disease progression ≥ 6 months (mo) after initiating ET + CDK4/6i in the LA/mBC setting (and ≥ 4 mo on most recent ET, if ET + CDK4/6i was not the most recent therapy received), or relapsed either while taking or within 12 mo of exposure to combination adjuvant ET (≥ 12 mo) + CDK4/6i (≥ 6 mo), and available blood sample for circulating tumor DNA central testing for
ESR1
m status. Men and pre-/perimenopausal women will receive a LHRH. Co-primary endpoints: Investigator-assessed progression-free survival (per RECIST v1.1) in the intent-to-treat and
ESR1
m populations. Secondary endpoints: Overall survival; objective response rate; duration of response; clinical benefit rate; pt-reported outcomes; safety; pharmacokinetics. Co-primary endpoint analyses will use a two-sided stratified log-rank test at an overall 0.05 significance level. An independent data monitoring committee will be in place for safety. Target enrollment is 320 pts, and this study is currently recruiting. Encore from SABCS 2022 (OT2-01-07). Clinical trial information: NCT05306340.
Clinical status
Clinical
1 clinical trial
14 organizations
5 drugs
4 targets
Clinical trial
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast CancerStatus: Recruiting, Estimated PCD: 2024-10-03
Organization
Dana-Farber Cancer InstituteOrganization
UPMC Hillman Cancer CenterOrganization
University of Pittsburgh Cancer InstituteOrganization
Memorial Sloan Kettering Cancer CenterOrganization
Hospital Gregorio MaranonOrganization
Universitaria Policlinico ModenaOrganization
National Center for Tumor Diseases (NCT)Organization
German Cancer Research CenterOrganization
The West Cancer CenterOrganization
GenentechOrganization
University of San FranciscoDrug
fulvestrantDrug
CDK4/6iDrug
everolimusDrug
exemestaneDrug
giredestrantTarget
ESR1 mutationTarget
CDK6Target
mTORC1Target
CDK4 & 6