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

Conditions

• Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• GDC-4198 — DRUG
  GDC-4198 will be administered orally.
• Giredestrant — DRUG
  Giredestrant will be administered orally.
• Abemaciclib — DRUG
  Abemaciclib will be administered orally.

Study Details

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.

Key Dates

Start date

Oct 7, 2025

Status verified

May 2026

Primary completion

Aug 31, 2028

Completion

Aug 31, 2028

Study Design

Enrollment

285 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• 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).
• 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).
• 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).
• 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).

Primary Outcome Measure

Phase Ib: Incidence and Severity of Adverse Events (AEs) [ Time Frame: Up to 36 months ]

Central Contacts

• Reference Study ID Number: GO46021 https://forpatients.roche.com/
  888-662-6728 (U.S. Only)
  [email protected]

Locations (16)

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