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.
Brief Title
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
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
888-662-6728 (U.S. Only)
Central Contact Email
global-roche-genentech-trials@gene.com
Central Contact Role
Contact
Completion Date
Completion Date Type
Estimated
Conditions
BREAST CANCER
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07100106
Org Class
Industry
Org Full Name
Genentech, Inc.
Org Study Id
GO46021
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
Severity of AEs determined according to the CTCAE v5.0 grading scale
Outcome Measure
Phase Ib: Incidence and Severity of Adverse Events (AEs)
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs)
Outcome Time Frame
From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days)
Outcome Measure
Phase II: Progression-free Survival (PFS)
Outcome Time Frame
Up to 36 months
Secondary Ids
Secondary Id
2025-521128-31-00
Secondary Id
2025
Secondary Outcomes
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase Ib: Objective Response Rate (ORR)
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase Ib: Clinical Benefit Rate (CBR)
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: ORR
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: Duration of Response (DOR)
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: CBR
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: Overall Survival (OS)
Outcome Time Frame
Month 6, Month 12
Outcome Measure
Phase II: OS Rate at 6 Months and 12 Months
Outcome Time Frame
Month 6, Month 12
Outcome Measure
Phase II: PFS Rate at 6 Months and 12 Months
Outcome Description
Severity of AEs determined according to the CTCAE v5.0 grading scale
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: Incidence and Severity of Adverse Events (AEs)
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: Plasma Concentration of GDC-4198
Outcome Time Frame
Up to 36 months
Outcome Measure
Phase II: Recommended Dose of GDC-4198
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sun Young Oh
Investigator Email
suyoung@montefiore.org
Investigator Phone
918-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Breast Cancer --- BREAST NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
MeSH Terms
BREAST NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
BREAST DISEASES
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
GIREDESTRANT
ABEMACICLIB