Recruiting NCT07100106
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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: GDC-4198, Giredestrant, Abemaciclib.
- Who it may be relevant to
- Registry conditions: Breast Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Brazil, Canada, China +5
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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
Overview
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.
Interventions
- Drug GDC-4198
GDC-4198 will be administered orally. - Drug Giredestrant
Giredestrant will be administered orally. - Drug Abemaciclib
Abemaciclib will be administered orally.
Primary outcome measures
- Phase Ib: Incidence and Severity of Adverse Events (AEs) [Time frame: Up to 36 months]
- Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs) [Time frame: From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days)]
- Phase II: Progression-free Survival (PFS) [Time frame: Up to 36 months]
Secondary outcome measures (11)
- Phase Ib: Objective Response Rate (ORR) [Time frame: Up to 36 months]
- Phase Ib: Clinical Benefit Rate (CBR) [Time frame: Up to 36 months]
- Phase II: ORR [Time frame: Up to 36 months]
- Phase II: Duration of Response (DOR) [Time frame: Up to 36 months]
- Phase II: CBR [Time frame: Up to 36 months]
- Phase II: Overall Survival (OS) [Time frame: Up to 36 months]
- Phase II: OS Rate at 6 Months and 12 Months [Time frame: Month 6, Month 12]
- Phase II: PFS Rate at 6 Months and 12 Months [Time frame: Month 6, Month 12]
- Phase II: Incidence and Severity of Adverse Events (AEs) [Time frame: Up to 36 months]
- Phase II: Plasma Concentration of GDC-4198 [Time frame: Up to 36 months]
- Phase II: Recommended Dose of GDC-4198 [Time frame: Up to 36 months]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 20 centers
- City of Hope — Duarte
- City of Hope - Orange County Lennar Foundation Cancer Center — Irvine
- UC San Diego Moores Cancer Center — La Jolla
- UCSF Helen Diller Family CCC — San Francisco
- Sylvester Comprehensive Cancer Center — Miami
- Moffitt Cancer Center — Tampa
- Winship Cancer Institute of Emory University — Atlanta
- City of Hope® Cancer Center Chicago — Zion
- … and 12 more centers
South Korea · 6 centers
- Gangnam Severance Hospital, Yonsei University Health System — Seoul
- Seoul National University Bundang Hospital — Seongnam-si
- Seoul National University Hospital — Seoul
- Asan Medical Center. — Seoul
- Severance Hospital, Yonsei University Health System — Seoul
- The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul
Brazil · 5 centers
- Hospital do Cancer de Pernambuco - HCP — Recife
- ONCOSITE Centro de Pesquisa Clínica Em Oncologia — Ijuí
- Irmandade Da Santa Casa de Misericordia de Porto Alegre — Porto Alegre
- Hospital de Clinicas de Porto Alegre (HCPA) - PPDS — Porto Alegre
- Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESP — São Paulo
France · 5 centers
- Institut Jean Godinot — Reims
- Gustave Roussy — Villejuif
- Centre Francois Baclesse — Caen
- Centre Oscar Lambret — Lille
- Centre Eugene Marquis — Rennes
Spain · 5 centers
- Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON — Barcelona
- Hospital Beata Maria Ana — Madrid
- Hospital General Universitario Gregorio Maranon — Madrid
- Hospital Universitario 12 de Octubre — Madrid
- Hospital Clinico Universitario de Valencia — Valencia
Italy · 4 centers
- IRCCS Azienda Ospedaliero Universitaria di Bologna — Bologna
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS — Meldola
- ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia — Brescia
- Ospedale San Raffaele S.r.l. - PPDS — Milan
Australia · 2 centers
- St Vincent's Hospital Sydney — Darlinghurst
- Cancer Research SA — Adelaide
China · 2 centers
- Shandong Cancer Hospital — Jinan
- Fudan University Shanghai Cancer Center - Pudong Campus — Shanghai
Germany · 2 centers
- KEM - Evang. Huyssens-Stiftung Essen-Huttrop — Essen
- Universitatsklinikum Hamburg-Eppendorf — Hamburg
Canada · 1 center
- Princess Margaret Hospital — Toronto
Identifiers
NCT: NCT07100106 · GO46021 · 2025-521128-31-00