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
Not Applicable
Recruiting
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT07100106
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 285
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 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 anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (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.
- Poor peripheral venous access
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase Ib: Dose-Finding Stage GDC-4198 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). Phase Ib: Dose-Finding Stage Giredestrant 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). Phase II: Arm A GDC-4198 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). Phase II: Arm A Giredestrant 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). Phase II: Arm B GDC-4198 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). Phase II: Arm B Giredestrant 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). Phase II: Arm C Giredestrant 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). Phase II: Arm C Abemaciclib 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).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Phase Ib: Objective Response Rate (ORR) Up to 36 months Phase Ib: Clinical Benefit Rate (CBR) Up to 36 months Phase Ib: Area Under the Concentration Time-Curve From Time 0 to Last Measurable Concentration (AUC0-t) of GDC-4198 Up to 36 months Phase Ib: Area Under the Concentration Time-Curve From Time 0 to Infinity (AUCinf) of GDC-4198 Up to 36 months Phase Ib: Maximum Serum Concentration (Cmax) of GDC-4198 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
Trial Locations
- Locations (1)
New York Cancer & Blood Specialists
🇺🇸East Patchogue, New York, United States
New York Cancer & Blood Specialists🇺🇸East Patchogue, New York, United States