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 (MoonROSE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: GDC-4198; Drug: Giredestrant; Drug: Abemaciclib

• Study Type: Interventional
• Enrollment (Estimated): 285
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO46021 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent's Hospital Sydney
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Cancer Research SA
• Brazil
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESP
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50040-000
      • Recruiting
      • Hospital do Cancer de Pernambuco - HCP
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Recruiting
      • ONCOSITE Centro de Pesquisa Clínica Em Oncologia
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-074
      • Recruiting
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-030
      • Recruiting
      • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Hospital
• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201321
      • Recruiting
      • Fudan University Shanghai Cancer Center - Pudong Campus
• France
  • Caen, France, 14076
    • Recruiting
    • Centre Francois Baclesse
  • Lille, France, 59020
    • Recruiting
    • Centre Oscar Lambret
  • Rennes, France, 35042
    • Recruiting
    • Centre Eugène Marquis
  • Champagne-Ardenne
    • Reims, Champagne-Ardenne, France, 51100
      • Recruiting
      • Institut Jean Godinot
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Recruiting
      • Gustave Roussy
• Germany
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45136
      • Recruiting
      • KEM - Evang. Huyssens-Stiftung Essen-Huttrop
• Italy
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Recruiting
      • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • Recruiting
      • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
• South Korea
  • Seongnam-si, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 3722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center.
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 6273
      • Recruiting
      • Gangnam Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital Beata Maria Ana
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope - Orange County Lennar Foundation Cancer Center
    • La Jolla, California, United States, 92093-1503
      • Recruiting
      • UC San Diego Moores Cancer Center
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Helen Diller Family CCC
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Recruiting
      • Winship Cancer Institute of Emory University
  • Illinois
    • Zion, Illinois, United States, 60099
      • Recruiting
      • City of Hope® Cancer Center Chicago
  • Maine
    • Detroit, Maine, United States, 48201-2013
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Recruiting
      • Washington University Siteman Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901-1914
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • New York
    • East Patchogue, New York, United States, 11772
      • Recruiting
      • New York Cancer & Blood Specialists
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213-3108
      • Recruiting
      • UPMC - Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37204-3609
      • Recruiting
      • Vanderbilt Breast Center at One Hundred Oaks
  • Texas
    • Dallas, Texas, United States, 75246-2003
      • Recruiting
      • Texas Oncology (Worth) - USOR
  • Virginia
    • Norfolk, Virginia, United States, 23502-2800
      • Recruiting
      • Virginia Oncology Associates (Norfolk) - USOR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ib: Dose-Finding Stage; Participants will receive GDC-4198 as monotherapy and in combination with giredestrant, 30 milligrams (mg), orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).	Drug: GDC-4198; GDC-4198 will be administered orally.; Other Names: RGT-419B; RO7840734; Drug: Giredestrant; Giredestrant will be administered orally.; Other Names: GDC-9545; RO7197597
Experimental: Phase II: Arm A; Participants will receive GDC-4198, higher dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).	Drug: GDC-4198; GDC-4198 will be administered orally.; Other Names: RGT-419B; RO7840734; Drug: Giredestrant; Giredestrant will be administered orally.; Other Names: GDC-9545; RO7197597
Experimental: Phase II: Arm B; Participants will receive GDC-4198, lower dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).	Drug: GDC-4198; GDC-4198 will be administered orally.; Other Names: RGT-419B; RO7840734; Drug: Giredestrant; Giredestrant will be administered orally.; Other Names: GDC-9545; RO7197597
Experimental: Phase II: Arm C; Participants will receive abemaciclib, 150 mg twice daily, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).	Drug: Giredestrant; Giredestrant will be administered orally.; Other Names: GDC-9545; RO7197597; Drug: Abemaciclib; Abemaciclib will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Incidence and Severity of Adverse Events (AEs)	Severity of AEs determined according to the CTCAE v5.0 grading scale	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Objective Response Rate (ORR)		Up to 36 months
Phase Ib: Clinical Benefit Rate (CBR)		Up to 36 months
Phase II: ORR		Up to 36 months
Phase II: Duration of Response (DOR)		Up to 36 months
Phase II: CBR		Up to 36 months
Phase II: Overall Survival (OS)		Up to 36 months
Phase II: OS Rate at 6 Months and 12 Months		Month 6, Month 12
Phase II: PFS Rate at 6 Months and 12 Months		Month 6, Month 12
Phase II: Incidence and Severity of Adverse Events (AEs)	Severity of AEs determined according to the CTCAE v5.0 grading scale	Up to 36 months
Phase II: Plasma Concentration of GDC-4198		Up to 36 months
Phase II: Recommended Dose of GDC-4198		Up to 36 months

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Roche (China) Holding Ltd.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: July 31, 2025
• First Submitted That Met QC Criteria: July 31, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; giredestrant; abemaciclib
• Other Study ID Numbers: GO46021; 2025-521128-31-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No