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

Purpose

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.

Condition

  • Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase Ib: Dose-Finding Stage 		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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
Experimental
Phase II: Arm A 		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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
Experimental
Phase II: Arm B 		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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
Experimental
Phase II: Arm C 		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).
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
  • Drug: Abemaciclib
    Abemaciclib will be administered orally.

Recruiting Locations

Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204-3609

More Details

Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: GO46021 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com

For general questions about clinical trials, contact Research Support Services at (615) 322-7343 or research.support.services@vumc.org