RecruitingRecruiting
A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer
NCT07100106 · Genentech, Inc.
In plain English
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Official title
A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor
About this study
The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus abemaciclib + giredestrant in participants with locally advanced or metastatic ER+, HER2- breast cancer. The study consists of 2 phases: Phase Ib and Phase II. Phase Ib will evaluate the safety and pharmacokinetics (PK) of GDC-4198 alone and in combination with giredestrant. Phase II stage will compare the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant.
Eligibility criteria
Inclusion Criteria:
* Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
* Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
* Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and approved endocrine therapy (ET) in the locally advanced or metastatic setting.
* Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Life expectancy \>= 6 months.
Exclusion Criteria:
* Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
* Have received more than one-line of therapy for locally advanced or metastatic disease.
* Have received prior chemotherapy for metastatic breast cancer.
* Treatment with an approved oral ET within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
* Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
* History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.
* Known allergy or hypersensitivity to any component of the study treatments.
Study design
Enrollment target: 285 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-10-07
Estimated completion: 2028-08-31
Last updated: 2026-07-13
Interventions
Drug: GDC-4198Drug: GiredestrantDrug: Abemaciclib
Primary outcomes
- • Phase Ib: Incidence and Severity of Adverse Events (AEs) (Up to 36 months)
- • Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs) (From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days))
- • Phase II: Progression-free Survival (PFS) (Up to 36 months)
Sponsor
Genentech, Inc. · industry
With: Roche (China) Holding Ltd.
Contacts & investigators
ContactReference Study ID Number: GO46021 https://forpatients.roche.com/ No attachments to email below. · contact · global-roche-genentech-trials@gene.com · 888-662-6728 (U.S. Only)
ContactFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry · contact
InvestigatorClinical Trials · study_director, Hoffmann-La Roche
All locations (52)
City of HopeRecruiting
Duarte, California, United States
City of Hope - Orange County Lennar Foundation Cancer CenterRecruiting
Irvine, California, United States
UC San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
UCSF Helen Diller Family CCCRecruiting
San Francisco, California, United States
Sylvester Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Winship Cancer Institute of Emory UniversityRecruiting
Atlanta, Georgia, United States
City of Hope® Cancer Center ChicagoRecruiting
Zion, Illinois, United States
Barbara Ann Karmanos Cancer InstituteRecruiting
Detroit, Maine, United States
Washington University Siteman Cancer CenterRecruiting
St Louis, Missouri, United States
Rutgers Cancer Institute of New JerseyRecruiting
New Brunswick, New Jersey, United States
New York Cancer & Blood SpecialistsRecruiting
East Patchogue, New York, United States
Levine Cancer InstituteRecruiting
Charlotte, North Carolina, United States
Novant Health Cancer InstituteRecruiting
Charlotte, North Carolina, United States
University of Pennsylvania - Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
UPMC - Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred OaksRecruiting
Nashville, Tennessee, United States
Texas Oncology (Worth) - USORRecruiting
Dallas, Texas, United States
University of Utah Huntsman Cancer InstituteRecruiting
Salt Lake City, Utah, United States
Virginia Oncology Associates (Norfolk) - USORRecruiting
Norfolk, Virginia, United States
St Vincent's Hospital SydneyRecruiting
Darlinghurst, New South Wales, Australia
Cancer Research SARecruiting
Adelaide, South Australia, Australia
Hospital do Cancer de Pernambuco - HCPRecruiting
Recife, Pernambuco, Brazil
ONCOSITE Centro de Pesquisa Clínica Em OncologiaRecruiting
Ijuí, Rio Grande do Sul, Brazil
Irmandade Da Santa Casa de Misericordia de Porto AlegreRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Hospital de Clinicas de Porto Alegre (HCPA) - PPDSRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESPRecruiting
São Paulo, Brazil
Princess Margaret HospitalRecruiting
Toronto, Ontario, Canada
Shandong Cancer HospitalRecruiting
Jinan, SD, China
Fudan University Shanghai Cancer Center - Pudong CampusRecruiting
Shanghai, Shanghai Municipality, China
Institut Jean GodinotRecruiting
Reims, Champagne-Ardenne, France
Gustave RoussyRecruiting
Villejuif, Val-de-Marne, France
Centre Francois BaclesseRecruiting
Caen, France
Centre Oscar LambretRecruiting
Lille, France
Centre Eugene MarquisRecruiting
Rennes, France
KEM - Evang. Huyssens-Stiftung Essen-HuttropRecruiting
Essen, North Rhine-Westphalia, Germany
Universitatsklinikum Hamburg-EppendorfRecruiting
Hamburg, Germany
IRCCS Azienda Ospedaliero Universitaria di BolognaRecruiting
Bologna, Emilia-Romagna, Italy
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDSRecruiting
Meldola, Emilia-Romagna, Italy
ASST degli Spedali Civili di Brescia - Spedali Civili di BresciaRecruiting
Brescia, Lombardy, Italy
Ospedale San Raffaele S.r.l. - PPDSRecruiting
Milan, Lombardy, Italy
Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, Seoul Teugbyeolsi, South Korea
Seoul National University Bundang HospitalRecruiting
Seongnam-si, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Asan Medical Center.Recruiting
Seoul, South Korea
Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's HospitalRecruiting
Seoul, South Korea
Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPONRecruiting
Barcelona, Spain
Hospital Beata Maria AnaRecruiting
Madrid, Spain
Hospital General Universitario Gregorio MaranonRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Clinico Universitario de ValenciaRecruiting
Valencia, Spain