Advanced or Metastatic Breast CancerPhase 1FrontROSENCT07867262
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
A Phase 1 study testing GDC-4198, Fulvestrant and Letrozole in people with Advanced or Metastatic Breast Cancer, run by Genentech, Inc..
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Breast Cancer
- What is being tested?
- GDC-4198, Fulvestrant and Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- No sites listed yet
- Study dates
- 15 Dec 2026to 15 Aug 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: GO46022 https://forpatients.roche.com/ No attachments to email below. contact
Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact
About this study
Official title: A Phase Ib, Multicenter, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Who Are Sensitive or Resistant to Endocrine Therapy
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
- Being tested
- GDC-4198, Fulvestrant, Letrozole, Giredestrant
- Keywords
- HR+ positive, HER2 negative breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDC-4198Drug
Also called RGT-419B, RO7840734
Participants will receive GDC-4198 as per the schedule described in the protocol.
FulvestrantDrug
Participants will receive fulvestrant as per the schedule described in the protocol.
LetrozoleDrug
Participants will receive letrozole as per the schedule described in the protocol.
GiredestrantDrug
Also called GDC-9545, RO7197597
Participants will receive giredestrant as per the schedule described in the protocol.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: GDC-4198; Drug: Giredestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Adverse Events (AEs)
Measured: Approximately 30 months
Secondary outcomes (3)
Plasma Concentration of GDC-4198
Measured: Approximately 30 months
Objective Response Rate (ORR)
Measured: Approximately 30 months
Clinical Benefit Rate (CBR)
Measured: Approximately 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2026
- Study start15 Dec 2026 (estimated)
- Primary completion15 Aug 2030 (estimated)
- Study completion15 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 165 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07867262
- Sponsor's protocol ID
- GO46022
- Other IDs
- 2026-525266-22-00
- Acronym
- FrontROSE
- Status last verified
- Nov 2026
- First submitted
- 5 Oct 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Multicenter, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Who Are Sensitive or Resistant to Endocrine Therapy
- ClinicalTrials.gov ID
- NCT07867262
- Acronym / sponsor ID
- FrontROSE / GO46022
- Conditions
- Advanced or Metastatic Breast Cancer
- Keywords
- HR+ positive, HER2 negative breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 165 participants (estimated)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Dec 2026 (estimated)
- Primary completion
- 15 Aug 2030 (estimated)
- Study completion
- 15 Aug 2030 (estimated)
- First posted
- 9 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GDC-4198 with fulvestrant | Experimental | Drug: GDC-4198, Drug: FulvestrantDuring 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. |
| GDC-4198 with letrozole | Experimental | Drug: GDC-4198, Drug: LetrozoleDuring 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. |
| GDC-4198 with giredestrant | Experimental | Drug: GDC-4198, Drug: GiredestrantDuring 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GDC-4198Also: RGT-419B, RO7840734Participants will receive GDC-4198 as per the schedule described in the protocol. | Drug | GDC-4198 with fulvestrant, GDC-4198 with giredestrant, GDC-4198 with letrozole |
| FulvestrantParticipants will receive fulvestrant as per the schedule described in the protocol. | Drug | GDC-4198 with fulvestrant |
| LetrozoleParticipants will receive letrozole as per the schedule described in the protocol. | Drug | GDC-4198 with letrozole |
| GiredestrantAlso: GDC-9545, RO7197597Participants will receive giredestrant as per the schedule described in the protocol. | Drug | GDC-4198 with giredestrant |
Primary outcome
Incidence and Severity of Adverse Events (AEs)
Time frame: Approximately 30 months
3 secondary outcomes
Plasma Concentration of GDC-4198
Time frame: Approximately 30 months
Objective Response Rate (ORR)
Time frame: Approximately 30 months
Clinical Benefit Rate (CBR)
Time frame: Approximately 30 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Reference Study ID Number: GO46022 https://forpatients.roche.com/ No attachments to email below. contact
Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact
Clinical Trials study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GDC-4198, Fulvestrant and Letrozole in people with Advanced or Metastatic Breast Cancer, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Reference Study ID Number: GO46022 https://forpatients.roche.com/ No attachments to email below. (888-662-6728, global-roche-genentech-trials@gene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Adverse Events (AEs) (time frame: Approximately 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.