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NCT Number: NCT07100106

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

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GDC-4198

Drug

GDC-4198 will be administered orally.

Other names: RGT-419B, RO7840734

Giredestrant

Drug

Giredestrant will be administered orally.

Other names: GDC-9545, RO7197597

Abemaciclib

Drug

Abemaciclib will be administered orally.

Primary outcomes

  1. Phase Ib: Incidence and Severity of Adverse Events (AEs)

    Time frame: Up to 36 months

    Severity of AEs determined according to the CTCAE v5.0 grading scale

  2. Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs)

    Time frame: From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days)

  3. Phase II: Progression-free Survival (PFS)

    Time frame: Up to 36 months

Secondary outcomes

  1. Phase Ib: Objective Response Rate (ORR)

    Time frame: Up to 36 months

  2. Phase Ib: Clinical Benefit Rate (CBR)

    Time frame: Up to 36 months

  3. Phase II: ORR

    Time frame: Up to 36 months

  4. Phase II: Duration of Response (DOR)

    Time frame: Up to 36 months

  5. Phase II: CBR

    Time frame: Up to 36 months

  6. Phase II: Overall Survival (OS)

    Time frame: Up to 36 months

  7. Phase II: OS Rate at 6 Months and 12 Months

    Time frame: Month 6, Month 12

  8. Phase II: PFS Rate at 6 Months and 12 Months

    Time frame: Month 6, Month 12

  9. Phase II: Incidence and Severity of Adverse Events (AEs)

    Time frame: Up to 36 months

    Severity of AEs determined according to the CTCAE v5.0 grading scale

  10. Phase II: Plasma Concentration of GDC-4198

    Time frame: Up to 36 months

  11. Phase II: Recommended Dose of GDC-4198

    Time frame: Up to 36 months

Study contacts

Contact information is provided by the study sponsor or research team.

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry

CONTACT

Reference Study ID Number: GO46021 https://forpatients.roche.com/ No attachments to email below.

CONTACT

[email protected]

888-662-6728 (U.S. Only)

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Collaborators

  • Roche (China) Holding Ltd.

Registry information

Official study title

A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

Acronym: MoonROSE

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Aug 3, 2025
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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