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Study of inavolisib, palbociclib and letrozole combination for patients with advanced hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutation

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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 advanced breast cancer that is hormone receptor-positive, HER2-negative, and has a specific genetic change called PIK3CA mutation. The research evaluates a combination treatment that includes three medications: inavolisib (also known as GDC-0077), letrozole, and a type of drug called a CDK4/6 inhibitor (palbociclib). Some participants will receive these active medications, while others will receive a placebo instead of inavolisib, along with the other treatments.

The main purpose is to determine how well the combination of inavolisib with letrozole and palbociclib works compared to using just letrozole and palbociclib with a placebo in treating this specific type of breast cancer. The study will measure how long participants remain without their cancer getting worse while receiving the treatment.

All medications in this study are taken by mouth in the form of tablets. The study will track various aspects of participants' health, including how well the treatment works, any side effects that may occur, and how the treatment affects their quality of life. This research is planned as a long-term study that will continue for several years to gather comprehensive information about the effectiveness and safety of this treatment combination.

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 assessment

    Your eligibility for the study will be confirmed through blood tests or existing tumor tissue analysis to check for PIK3CA mutation

    Medical evaluation will be performed to verify measurable disease using RECIST criteria (a standardized way to measure tumors)

    Laboratory tests will be conducted to check blood counts and organ function

  2. Step 2

    Treatment assignment

    You will be randomly assigned to one of two treatment groups

    Group 1: Inavolisib + CDK4/6 inhibitor (Palbociclib) + Letrozole

    Group 2: Placebo + CDK4/6 inhibitor (Palbociclib) + Letrozole

  3. Step 3

    Treatment administration

    All medications will be taken by mouth in tablet form

    If you are premenopausal or a male patient, you will also receive hormone therapy (LHRH agonist)

    Regular assessments will monitor your tumor response to treatment

  4. Step 4

    Monitoring and evaluation

    Regular checks of vital signs and laboratory tests

    Assessment of any side effects using standardized criteria

    Completion of quality of life questionnaires about pain, physical function, and treatment side effects

    Regular imaging to measure tumor response

  5. Step 5

    Follow-up period

    Continued monitoring until disease progression or other stopping criteria are met

    Assessment of long-term treatment effects

    Documentation of any side effects or health changes

Who can join the trial?

10 criteria

  • You must have hormone receptor-positive (HR+) and HER2-negative advanced breast cancer that is either:
    • Newly diagnosed, or
    • Returned after at least 2 years of standard hormone therapy treatment
    • If you previously received CDK4/6 inhibitor treatment (a type of targeted therapy), your cancer must not have progressed during treatment or within 1 year after stopping it
    • You must have a confirmed PIK3CA mutation (a specific genetic change) in your blood or tumor tissue through testing
    • Your cancer must be measurable using standard imaging criteria (RECIST v1.1)
    • You can be:
      • A man of any age
      • A woman who has gone through menopause
      • A woman who has not gone through menopause or is going through menopause
      • If you are a man or a woman who has not completed menopause, you must be willing to receive hormone-blocking therapy (LHRH agonist) throughout the study
      • Your blood tests and organ function tests must show acceptable results within 14 days before starting the study treatment

Who cannot join the trial?

13 criteria

  • Prior treatment with a PI3K inhibitor (a type of targeted cancer therapy)
  • Active brain metastases (cancer that has spread to the brain) or spinal cord compression
  • History of diabetes requiring insulin treatment
  • Severe heart conditions, including:
    • Unstable angina (chest pain)
    • Heart attack within the past 6 months
    • Uncontrolled high blood pressure
    • Significant liver problems or active hepatitis B or C infection
    • Known allergic reactions to similar medications
    • Pregnant or breastfeeding women
    • Any other serious medical condition that could affect study participation
    • Current participation in another clinical trial
    • Unable to swallow oral medications
    • History of other cancers within the past 5 years (except adequately treated non-melanoma skin cancer or cervical cancer in situ)
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Investigated drugs

  • Inavolisib

    is a medication that targets specific mutations in breast cancer cells, particularly those with PIK3CA mutations. It works by blocking certain proteins that can contribute to cancer growth. This medication is being studied as a new treatment option for advanced breast cancer.

  • Letrozole

    is a hormone therapy medication that works by reducing the amount of estrogen produced in the body. It is commonly used to treat hormone receptor-positive breast cancer in postmenopausal women.

  • CDK4/6 inhibitor

    is a type of targeted therapy that blocks specific proteins called CDK4 and CDK6, which help control cell growth. These medications help slow down or stop the growth of cancer cells and are already approved for treating certain types of breast cancer.

What is already known about the treatment

  • Inavolisib

    An investigational oral medication being studied in clinical trials for PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer. It works by inhibiting the phosphatidylinositol 3-kinase (PI3K) pathway, which is often overactive in breast cancer cells with PIK3CA mutations. The drug is being tested in combination with CDK4/6 inhibitors and letrozole as a targeted therapy approach for breast cancer treatment.

  • Letrozole

    An oral medication belonging to the class of aromatase inhibitors that is used in the treatment of hormone receptor-positive breast cancer. It works by blocking the enzyme aromatase, which is responsible for producing estrogen in postmenopausal women, thereby reducing estrogen levels that can fuel breast cancer growth. The drug is commonly used as a standard treatment in hormone-dependent breast cancer therapy.

  • CDK4/6 Inhibitors

    A class of oral medications that target specific proteins called cyclin-dependent kinases 4 and 6, which play a crucial role in cell division. These drugs work by blocking these proteins to help stop cancer cells from dividing and growing. They are typically used in combination with hormone therapy for treating hormone receptor-positive, HER2-negative advanced breast cancer.

Investigated diseases

PIK3CA-Mutated Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer - A specific type of breast cancer characterized by mutations in the PIK3CA gene and the presence of hormone receptors, while lacking HER2 protein overexpression. This cancer develops when breast cells acquire specific genetic changes in the PIK3CA gene, which affects cell growth and division. The cancer cells in this type respond to hormones like estrogen and progesterone but do not have excessive amounts of HER2 protein on their surface. This form of breast cancer typically grows and spreads more slowly than some other types. The disease can spread beyond the breast to other parts of the body, while maintaining its original characteristics.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-516162-11-00Protocol codeWO45654Estimated enrolment450 patientsSponsorF. Hoffmann-La Roche AG

sourced from the EU Clinical Trials Register and site verification

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