Breast Cancer
Conditions
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.
Interventions
DRUGGDC-4198
GDC-4198 will be administered orally.
DRUGGiredestrant
Giredestrant will be administered orally.
DRUGAbemaciclib
Abemaciclib will be administered orally.
Sponsors
Genentech, Inc.
Roche (China) Holding Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Incidence and Severity of Adverse Events (AEs) | Up to 36 months | Severity of AEs determined according to the CTCAE v5.0 grading scale |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 36 months | Severity of AEs determined according to the CTCAE v5.0 grading scale |
| Phase II: Plasma Concentration of GDC-4198 | Up to 36 months | — |
| Phase II: Recommended Dose of GDC-4198 | Up to 36 months | — |
Countries
Australia, Brazil, Canada, France, Germany, Italy, South Korea, Spain, United States
Contacts
CONTACTReference Study ID Number: GO46021 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed