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 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GO460212025-521128-31-00
• Study Type: interventional
• Target: 285
• Locations: 8 countries
• Sites: 35

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• 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

Study Arms (4)

Phase Ib: Dose-Finding Stage

EXPERIMENTAL

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; Drug: Giredestrant

Phase II: Arm A

EXPERIMENTAL

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; Drug: Giredestrant

Phase II: Arm B

EXPERIMENTAL

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; Drug: Giredestrant

Phase II: Arm C

EXPERIMENTAL

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; Drug: Abemaciclib

Interventions

GDC-4198 DRUG

GDC-4198 will be administered orally.

Also known as: RGT-419B, RO7840734

Phase II: Arm A; Phase II: Arm B; Phase Ib: Dose-Finding Stage

Giredestrant DRUG

Giredestrant will be administered orally.

Also known as: GDC-9545, RO7197597

Phase II: Arm A; Phase II: Arm B; Phase II: Arm C; Phase Ib: Dose-Finding Stage

Abemaciclib DRUG

Abemaciclib will be administered orally.

Phase II: Arm C

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genentech, Inc.: lead
• Roche (China) Holding Ltd.: collaborator

Study Sites (35)

City of Hope

Duarte, California, 91010, United States

RECRUITING

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

RECRUITING

UCSF Helen Diller Family CCC

San Francisco, California, 94158, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322-1013, United States

RECRUITING

City of Hope® Cancer Center Chicago

Zion, Illinois, 60099, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Maine, 48201-2013, United States

RECRUITING

Washington University Siteman Cancer Center

St Louis, Missouri, 63110-1010, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901-1914, United States

RECRUITING

New York Cancer & Blood Specialists

East Patchogue, New York, 11772, United States

RECRUITING

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213-3108, United States

RECRUITING

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204-3609, United States

RECRUITING

Texas Oncology (Worth) - USOR

Dallas, Texas, 75246-2003, United States

RECRUITING

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Cancer Research SA

Adelaide, South Australia, 5000, Australia

RECRUITING

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, 50040-000, Brazil

RECRUITING

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

RECRUITING

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Institut Jean Godinot

Reims, Champagne-Ardenne, 51100, France

RECRUITING

Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

RECRUITING

Centre Francois Baclesse

Caen, 14076, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

RECRUITING

KEM - Evang. Huyssens-Stiftung Essen-Huttrop

Essen, North Rhine-Westphalia, 45136, Germany

RECRUITING

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 6273, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

RECRUITING

Asan Medical Center.

Seoul, 05505, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

RECRUITING

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, 08035, Spain

RECRUITING

Hospital Beata Maria Ana

Madrid, 28007, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; abemaciclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GO46021 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 3, 2025
• Study Start: October 7, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (5); FR (5); AU (2); US (14); CA (1); DE (1); BR (2); KR (5)