A Study to Evaluate the Effects of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Participants With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negatve Breast Cancer

NCT07867262 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: GO460222026-525266-22-00
• Study Type: interventional
• Target: 165
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study will evaluate the safety, pharmacokinetics, and preliminary activity of GDC-4198 when given in combination with endocrine therapy (ET) (letrozole, fulvestrant, or giredestrant) as first-line treatment to participants with locally advanced or metastatic Hormone receptor (HR)-positive, Human epidermal growth factor receptor-2 (HER2)-negative breast cancer

Conditions

Advanced or Metastatic Breast Cancer

Keywords

HR+ positive; HER2 negative breast cancer

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Adverse Events (AEs)

  Approximately 30 months

Secondary Outcomes (3)

• Plasma Concentration of GDC-4198

  Approximately 30 months

• Objective Response Rate (ORR)

  Approximately 30 months

• Clinical Benefit Rate (CBR)

  Approximately 30 months

Study Arms (3)

GDC-4198 with fulvestrant

EXPERIMENTAL

During safety run-in stage, participants will receive GDC-4198, higher dose in combination with fulvestrant, as per a pre-defined dosing regimen during Cycle 1 (1 cycle=28 days). During expansion stage, participants will receive GDC-4198, either lower or higher dose in combination with fulvestrant, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression.

Drug: GDC-4198; Drug: Fulvestrant

GDC-4198 with letrozole

EXPERIMENTAL

During expansion stage, participants will receive GDC-4198, either lower or higher dose in combination with letrozole, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression.

Drug: GDC-4198; Drug: Letrozole

GDC-4198 with giredestrant

EXPERIMENTAL

During expansion stage, participants will receive GDC-4198, either lower or higher dose in combination with giredestrant, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression.

Drug: GDC-4198; Drug: Giredestrant

Interventions

GDC-4198 DRUG

Participants will receive GDC-4198 as per the schedule described in the protocol.

Also known as: RGT-419B, RO7840734

GDC-4198 with fulvestrant; GDC-4198 with giredestrant; GDC-4198 with letrozole

Fulvestrant DRUG

Participants will receive fulvestrant as per the schedule described in the protocol.

GDC-4198 with fulvestrant

Letrozole DRUG

Participants will receive letrozole as per the schedule described in the protocol.

GDC-4198 with letrozole

Giredestrant DRUG

Participants will receive giredestrant as per the schedule described in the protocol.

Also known as: GDC-9545, RO7197597

GDC-4198 with giredestrant

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and HER2-negative disease.
• Disease documented HER2-negative tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines or documented ER-positive tumor according to ASCO/CAP guidelines.
• Measurable and/or non-measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) (including bone-only disease).
• For females \<= 60 years of age who are not in a postmenopausal state and males: initiation of treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy prior to initiation of study treatment according to clinical practice for the selected agent (preferably at least 14 days prior to initiation of study treatment), and agreement to continue LHRH agonist therapy for the duration of the study. LHRH agonist therapy may be discontinued in women \> 60 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy \>= 6 months.
• Participants with Endocrine therapy (ET)-resistant disease and ET-sensitive disease as defined in the protocol.

You may not qualify if:

• Advanced, symptomatic, visceral spread at the time of study entry that is at risk of life-threating complications and for which treatment with cytotoxic chemotherapy is considered appropriate per local treatment guidelines.
• Symptomatic, untreated, or actively progressing CNS metastases.
• History of systemic anti-cancer therapy for unresectable locally advanced breast cancer or metastatic breast cancer.
• 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

Related 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.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; Letrozole; giredestrant

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; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GO46022 https://forpatients.roche.com/ No attachments to email below.

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry

CONTACT

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: October 5, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): December 15, 2026
• Primary Completion (Estimated): August 15, 2030
• Study Completion (Estimated): August 15, 2030
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share