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Study comparing giredestrant plus palbociclib versus letrozole plus palbociclib in patients with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on treating estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer. This type of breast cancer has spread beyond the initial tumor site and shows specific characteristics that help determine the most effective treatment approach. The study compares two treatment combinations: giredestrant (also known as GDC-9545) with palbociclib versus letrozole with palbociclib. These medications are taken as oral capsules or tablets.

The purpose of the study is to evaluate how well giredestrant combined with palbociclib works compared to letrozole combined with palbociclib in treating this specific type of breast cancer. Some participants will receive the actual medications, while others will receive placebo versions of either giredestrant or letrozole along with palbociclib.

During the study, participants will take their assigned medications daily according to a specific schedule. The treatment period lasts for approximately 82 weeks. Throughout the study, doctors will monitor participants' health status and how their cancer responds to treatment through various medical examinations and tests.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment assignment

    You will be randomly assigned to one of two treatment groups:

    Group 1: giredestrant (taken orally) combined with palbociclib (taken orally)

    Group 2: letrozole (taken orally) combined with palbociclib (taken orally)

  2. Step 2

    Medication schedule

    If assigned to Group 1:

    - Take giredestrant capsules daily

    - Take palbociclib capsules (available in 75mg, 100mg, or 125mg strengths) as prescribed

    If assigned to Group 2:

    - Take letrozole 2.5mg film-coated tablets daily

    - Take palbociclib capsules (available in 75mg, 100mg, or 125mg strengths) as prescribed

  3. Step 3

    Regular monitoring

    Your condition will be regularly monitored for:

    - Changes in tumor size and disease progression

    - Pain levels and how it affects daily activities

    - Physical ability to perform daily tasks

    - Overall health status and quality of life

    - Any side effects or adverse reactions to the medication

  4. Step 4

    Additional requirements

    If you are a woman who is premenopausal or perimenopausal, or if you are a man:

    You will need to receive LHRH agonist therapy (a hormone therapy) throughout the study treatment period

  5. Step 5

    Study duration

    The study continues until March 2027 or until any of these occur:

    - Your disease shows progression

    - You experience unacceptable side effects

    - Your doctor decides to discontinue your participation

    - You choose to withdraw from the study

Who can join the trial?

9 criteria

  • You must be diagnosed with locally advanced or metastatic breast cancer that is estrogen receptor-positive and HER2-negative
  • Your cancer must be measurable through standard imaging tests (RECIST criteria) or have at least one bone lesion that can be monitored by CT or MRI scans
  • You must not have received any previous systemic treatment (medication that travels through the bloodstream) for advanced or metastatic breast cancer
  • If you had early-stage breast cancer previously, you must have:
    • Received at least 24 months of hormone therapy
    • Not had disease progression during that treatment
    • Had at least 12 months without disease after completing treatment
    • You must have good physical functioning ability (ECOG Performance Status of 0 or 1, meaning you can perform daily activities with minimal assistance)
    • If you are a premenopausal or perimenopausal woman, or a man, you must be willing to receive LHRH agonist therapy (medication that suppresses hormone production) throughout the study
    • Your cancer must not be curable with standard treatments

Who cannot join the trial?

14 criteria

  • History of prior treatment with any CDK4/6 inhibitor (medications that block specific proteins involved in cell growth)
  • Active brain or spinal cord metastases (cancer that has spread to these areas)
  • History of other cancers within the last 5 years, except for adequately treated non-melanoma skin cancer or cervical cancer
  • Significant heart conditions including:
    • Unstable angina (chest pain)
    • Recent heart attack
    • Severe heart rhythm problems
    • Severe liver problems or abnormal liver function tests
    • Known hypersensitivity (allergic reaction) to any of the study medications
    • Pregnancy or breastfeeding
    • Unable to swallow oral medications
    • Current participation in another clinical trial with experimental treatment
    • Any condition that, in the opinion of the study doctor, would interfere with safe participation in the study
    • Major surgery within 4 weeks before starting the study treatment
    • Serious infections requiring treatment, including active hepatitis B, hepatitis C, or HIV
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Investigated drugs

  • GDC-9545

    is an investigational medication being studied for treating breast cancer. It belongs to a class of drugs that work by targeting estrogen receptors in cancer cells. This medication is being tested as a potential new treatment option for patients with breast cancer that is estrogen receptor-positive and HER2-negative.

  • Palbociclib

    is a medication that works by blocking certain proteins (CDK4/6) that are involved in cell division. It helps slow down or stop the growth of cancer cells. It is already approved for treating certain types of breast cancer and is being used in combination with other treatments in this study.

  • Letrozole

    is a medication that belongs to a group of drugs called aromatase inhibitors. It works by reducing the amount of estrogen produced in the body, which can help slow or stop the growth of certain breast cancers that need estrogen to grow. It is commonly used to treat breast cancer in postmenopausal women.

What is already known about the treatment

  • GDC-9545

    An investigational oral selective estrogen receptor degrader (SERD) being studied in clinical trials for the treatment of estrogen receptor-positive, HER2-negative advanced breast cancer. This medication works by binding to and degrading estrogen receptors in cancer cells, potentially blocking tumor growth. It is being evaluated in combination with palbociclib as a potential alternative to existing treatments.

  • Palbociclib

    An oral targeted therapy that works as a selective inhibitor of cyclin-dependent kinases (CDK) 4 and 6, which are proteins involved in cell division. This medication is approved for treating hormone receptor-positive, HER2-negative advanced breast cancer in combination with hormone therapy. It helps block cancer cell growth by preventing cells from dividing.

  • Letrozole

    An oral aromatase inhibitor that blocks the production of estrogen in postmenopausal women. This medication is widely used in the treatment of hormone receptor-positive breast cancer and works by reducing the amount of estrogen available to stimulate cancer cell growth. It is commonly prescribed in combination with other targeted therapies like palbociclib.

Investigated diseases

Breast Cancer (Estrogen Receptor-Positive, HER2-Negative) - A specific type of breast cancer that grows in response to the hormone estrogen but does not have high levels of a protein called HER2. This cancer begins when cells in the breast tissue start to grow abnormally and multiply uncontrollably. The cancer cells have receptors that allow them to use estrogen to grow. In locally advanced cases, the cancer has spread to nearby tissues or lymph nodes but not to distant parts of the body. When metastatic, the cancer has spread beyond the breast and nearby lymph nodes to other parts of the body.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-506911-16-00Protocol codeBO41843Estimated enrolment1 241 patientsSponsorF. Hoffmann-La Roche AG

sourced from the EU Clinical Trials Register and site verification

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