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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
GroupInterventionDescription
Phase Ib: Dose-Finding StageGDC-4198Participants 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 StageGiredestrantParticipants 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 AGDC-4198Participants 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 AGiredestrantParticipants 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 BGDC-4198Participants 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 BGiredestrantParticipants 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 CGiredestrantParticipants 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 CAbemaciclibParticipants 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
NameTimeMethod
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
NameTimeMethod
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-4198Up to 36 months
Phase Ib: Area Under the Concentration Time-Curve From Time 0 to Infinity (AUCinf) of GDC-4198Up to 36 months
Phase Ib: Maximum Serum Concentration (Cmax) of GDC-4198Up to 36 months
Phase II: ORRUp to 36 months
Phase II: Duration of Response (DOR)Up to 36 months
Phase II: CBRUp to 36 months
Phase II: Overall Survival (OS)Up to 36 months
Phase II: OS Rate at 6 Months and 12 MonthsMonth 6, Month 12
Phase II: PFS Rate at 6 Months and 12 MonthsMonth 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-4198Up 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

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