A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)

NCT04576455 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: WO423122020-001984-10
• Study Type: interventional
• Target: 303
• Locations: 17 countries
• Sites: 80

Brief Summary

This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant compared with physician's choice of endocrine monotherapy in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced or metastatic setting.

Conditions

Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

  PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Kaplan-Meier methodology was used to estimate median PFS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months)

Secondary Outcomes (15)

• Overall Survival (OS)

  From randomization to death from any cause (duration of follow-up, median [range]: 34.6 [0.0-41.8] months)

• Objective Response Rate, as Determined by the Investigator According to RECIST v1.1

  From randomization until disease progression or death (up to approximately 15 months)

• Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1

  From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 15 months)

• Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1

  From randomization until disease progression or death (up to approximately 15 months)

• Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor (ESR1) Mutation Status

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months)

Study Arms (2)

Giredestrant

EXPERIMENTAL

Drug: Giredestrant; Drug: LHRH Agonist

Physician Choice of Endocrine Monotherapy

ACTIVE COMPARATOR

The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.

Drug: Fulvestrant or an Aromatase Inhibitor (Physician Choice); Drug: LHRH Agonist

Interventions

LHRH Agonist DRUG

Only premenopausal/perimenopausal participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

Giredestrant; Physician Choice of Endocrine Monotherapy

Giredestrant DRUG

Giredestrant is taken orally once per day on Days 1-28 of each 28-day cycle.

Also known as: GDC-9545, RO7197597, RG6171

Giredestrant

Fulvestrant or an Aromatase Inhibitor (Physician Choice) DRUG

Physician choice of endocrine monotherapy (fulvestrant or an aromatase inhibitor) is taken in accordance with the local prescribing information for the respective product.

Physician Choice of Endocrine Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who are postmenopausal or premenopausal/perimenopausal
• For women who are premenopausal or perimenopausal and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy for the duration of study treatment
• Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
• Documented ER-positive tumor and HER2-negative tumor, assessed locally
• Disease progression after treatment with one or two lines of systemic therapy (but not more than one prior targeted therapy) in the locally advanced or metastatic setting
• Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Adequate organ function

You may not qualify if:

• Prior treatment with a selective estrogen receptor degrader (SERD), with the exception of fulvestrant, if fulvestrant treatment was terminated at least 28 days prior to randomization
• Treatment with any investigational therapy within 28 days prior to randomization
• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Active cardiac disease or history of cardiac dysfunction
• Pregnant or breastfeeding

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (80)

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Northwest Cancer Specialists - Portland (SW Barnes Rd)

Tigard, Oregon, 97223, United States

Location

Instituto Angel Roffo

Buenos Aires, 1417, Argentina

Location

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, C1125ABD, Argentina

Location

Fundación Scherbovsky

Mendoza, M5500AYB, Argentina

Location

Hosp Provincial D. Centenarios

Rosario, S2002KDS, Argentina

Location

Organizacion Medica de Investigacion

San Nicolás, C1015ABO, Argentina

Location

Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Pronutrir - suporte nutricional e quimioterapia ltda.

Fortaleza, Ceará, 60810-180, Brazil

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo, 01317-001, Brazil

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Linyishi Cancer Hospital

Linyi, 276034, China

Location

The Third Hospital of Nanchang

Nanchang, 330000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche

Berlin, 14169, Germany

Location

Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem

Hamburg, 20357, Germany

Location

St. Vincenz-Krankenhaus Paderborn

Paderborn, 33098, Germany

Location

Gynäkologie Kompetenzzentrum

Stralsund, 18439, Germany

Location

Assuta Medical Center- Ashdod

Ashdod, Israel

Location

Hadassah Ein Karem Hospital

Jerusalem, 9112000, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Bialostockie Centrum Onkologii

Bialystok, 15-027, Poland

Location

Narodowy Instytut Onkologii Odzia? w Gliwicach

Gliwice, 44-102, Poland

Location

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad

Warsaw, 02-781, Poland

Location

Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky

Krasnoyarsk, Krasnodarskiy Kray, 660133, Russia

Location

Petrov Research Inst. of Oncology

Pesochny, Leningrad, 197758, Russia

Location

Blokhin Cancer Research Center

Moskva, Moscow Oblast, 115478, Russia

Location

Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod

Nizhny Novgorod, Niznij Novgorod, 603081, Russia

Location

St. Petersburg SHI "City Clinical Oncology Dispensary"

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic

Kazan', Tatarstan Republic, 420029, Russia

Location

Clinical Oncology Centre # 1

Krasnodar, 350040, Russia

Location

Multidisciplinary clinic Reaviz

Samara, 443011, Russia

Location

Volgograd Regional Clinical Oncology Dispensary

Volgograd, 400138, Russia

Location

Regional Clinical Oncology Hospital

Yaroslavl, 150040, Russia

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Iatros International

Bloemfontein, 9301, South Africa

Location

Eastleigh Breast Care Centre

Pretoria, 0081, South Africa

Location

Soon Chun Hyang University Cheonan Hospital

Dongnam-gu, Cheonan-si, 31151, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

National Cheng Kung Uni Hospital

Tainan, 704, Taiwan

Location

Chi-Mei Medical Centre

Tainan, 710, Taiwan

Location

Veterans General Hospital

Taipei, 00112, Taiwan

Location

Chang Gung Memorial Hosipital at Linkou

Taoyuan Hsien, 333, Taiwan

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Rajavithi Hospital

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Maharaj Nakorn Chiang Mai Hosp

Chang Mai, 50200, Thailand

Location

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Memorial Antalya Hospital

Antalya, 07020, Turkey (Türkiye)

Location

Dicle University Faculty of Medicine

Diyarbakır, 21280, Turkey (Türkiye)

Location

Kartal Dr Lutfi Kirdar Sehir Hastanesi

Istanbul, 34000, Turkey (Türkiye)

Location

Prof. Dr. Cemil Tascioglu City Hospital

Istanbul, 34384, Turkey (Türkiye)

Location

Izmir Ataturk Training and Research Hospital

Izmir, 35360, Turkey (Türkiye)

Location

Medikal Park Samsun

Samsun, 55200, Turkey (Türkiye)

Location

Zhytomyr Regional Oncology Center

Zhytomyr, KIEV Governorate, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 03115, Ukraine

Location

MI Kyiv Regional Council Kyiv Regional Oncological Dispensary

Kyiv, 04107, Ukraine

Location

RCI Sumy Regional Clinical Oncological Dispensary

Sumy, 40005, Ukraine

Location

Princess Alexandra Hospital

Harlow, CM20 1QX, United Kingdom

Location

Guys & St Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Peterborough City Hospital

Peterborough, PE3 9GZ, United Kingdom

Location

Related Publications (2)

• Martin M, Lim E, Chavez-MacGregor M, Bardia A, Wu J, Zhang Q, Nowecki Z, Cruz FM, Safin R, Kim SB, Schem C, Montero AJ, Khan S, Bandyopadhyay R, Moore HM, Shivhare M, Patre M, Martinalbo J, Roncoroni L, Perez-Moreno PD, Sohn J; acelERA Breast Cancer Study Investigators. Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study. J Clin Oncol. 2024 Jun 20;42(18):2149-2160. doi: 10.1200/JCO.23.01500. Epub 2024 Mar 27.

  PMID: 38537155 DERIVED

• Malhi V, Nowicka M, Chen YC, Agarwal P, Waldvogel M, Lien YTK, Hafner M, Perez-Moreno P, Moore HM, Yu J. UGT1A4 Polymorphism is not Associated with a Clinically Relevant Change in Giredestrant Exposure. Cancer Chemother Pharmacol. 2024 Jul;94(1):117-122. doi: 10.1007/s00280-023-04634-4. Epub 2024 Feb 2.

  PMID: 38305868 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; Fulvestrant; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Study Start: November 27, 2020
• Primary Completion: February 18, 2022
• Study Completion (Estimated): August 25, 2027
• Last Updated: March 20, 2026
• Results First Posted: March 10, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (3); UA (4); CN (9); ZA (2); BR (4); AU (2); TH (4); RU (10); DE (5); TW (5); PL (3); IL (3); KR (7); TU (8); AR (5); SG (2); GB (4)