RightFit
RecruitingPhase 1 / Phase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of GDC-4198 alone and with giredestrant. It also compares GDC-4198 plus giredestrant with abemaciclib plus giredestrant to see how safe they are and how well they work. It is for people with ER-positive, HER2-negative breast cancer that has spread nearby or to other parts of the body.

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. Participants from Study RGT-419B\_01-101 (NCT05304962) who are experiencing clinical benefit with GDC-4198, as determined by the investigator, may enroll in this study and continue receiving GDC-4198 at their current dose level following closure of Study RGT-419B\_01-101.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Tests confirm breast cancer called adenocarcinoma that has spread nearby or to other parts of the body.
  • The cancer is ER-positive (uses estrogen to grow) and HER2-negative (does not have high levels of the HER2 protein).
  • The cancer got worse during or after hormone therapy and a CDK4/6 inhibitor, a drug that blocks cancer cell growth, for advanced cancer.
  • The study team can check the cancer using standard rules, even if it cannot be measured.
  • You can do all usual activities, or can do light work but not heavy physical activity.
  • You are expected to live at least 6 months.
  • People in study RGT-419B_01-101 may join and keep taking their current GDC-4198 dose after that study closes if their doctor says it is helping.

Who can't join

  • Cancer has spread to internal organs, causes symptoms, and may soon be life-threatening, making chemotherapy the right treatment now.
  • You have had more than one course of treatment for cancer that has spread nearby or farther away.
  • You have had chemotherapy for breast cancer that spread to other parts of the body.
  • You took an approved hormone therapy pill within 7 days before starting the study drug, or fulvestrant or an approved CDK4/6 inhibitor within 21 days.
  • You have a digestive condition or have had surgery that could greatly limit how well your body absorbs the study drug.
  • You had another cancer within 3 years before screening, unless it has a very low risk of spreading or causing death.
  • You have a known allergy to any part of the study treatments.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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. * Current participant enrolled in Study RGT-419B\_01-101 who is experiencing clinical benefit from GDC-4198, as determined by the investigator, at the time of consent and enrollment in this study. 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 sites (33)

AL

AZ

CA

CO

FL

GA

IL

MA

MD

ME

MO

NC

NJ

NY

OH

OR

PA

TN

TX

UT

VA