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Comparing inavolisib plus fulvestrant versus alpelisib plus fulvestrant in patients with advanced hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutation

Verified siteRegistered drugNo placebo
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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 hormone receptor-positive, HER2-negative, PIK3CA mutated, locally advanced or metastatic breast cancer that has progressed during or after previous treatments. The study compares two treatment combinations: inavolisib plus fulvestrant versus alpelisib plus fulvestrant. These medications belong to a class of drugs called kinase inhibitors that work by blocking specific proteins involved in cancer growth.

The main purpose of this research is to determine how well inavolisib combined with fulvestrant works compared to alpelisib combined with fulvestrant in treating this specific type of breast cancer. The study will measure how long patients live without their cancer getting worse. Other aspects being studied include overall survival time, how well tumors respond to treatment, and how the treatments affect patients' quality of life.

Participants will receive either inavolisib or alpelisib pills taken by mouth daily, along with fulvestrant given as an intramuscular injection. During the study, patients will have regular medical check-ups and tests to monitor their cancer and any side effects from the treatment. The effectiveness of the treatment will be assessed through various medical examinations and imaging 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 medication assignment

    You will be randomly assigned to receive one of two treatment combinations:

    Group 1: Inavolisib tablets taken by mouth plus Fulvestrant given as an intramuscular injection

    Group 2: Alpelisib (Piqray) tablets taken by mouth plus Fulvestrant given as an intramuscular injection

  2. Step 2

    Treatment schedule

    You will take your assigned oral medication (either Inavolisib or Alpelisib) daily

    Fulvestrant injections will be administered at scheduled clinic visits

    Your doctor will determine the specific dosing schedule based on your treatment group

  3. Step 3

    Regular monitoring

    Your cancer progression will be regularly assessed through imaging scans

    Blood tests will be performed to monitor your health and medication levels

    Your doctor will evaluate any side effects you may experience

    You will complete questionnaires about your pain levels and daily activities

  4. Step 4

    Ongoing assessments

    Regular checks of your physical condition and ability to perform daily activities

    Monitoring of your overall health status

    Assessment of how well the treatment is working against your cancer

  5. Step 5

    Treatment duration

    Treatment will continue as long as your cancer does not worsen

    Your doctor may adjust or stop treatment based on how your body responds

    The study is planned to continue until March 2029

Who can join the trial?

10 criteria

  • You must have advanced breast cancer (metastatic adenocarcinoma) that cannot be treated with surgery or radiation therapy alone
  • Your breast cancer must be hormone receptor-positive and HER2-negative, confirmed by laboratory testing
  • Your tumor must have specific genetic changes (mutations) in the PIK3CA gene, which will be confirmed by a special test
  • You must have previously received treatment with:
    • A combination of hormone therapy and CDK4/6 inhibitor (a type of targeted therapy)
    • No more than 2 previous treatments for metastatic breast cancer
    • You may have had one course of chemotherapy for metastatic breast cancer
    • Your cancer must be measurable or able to be evaluated by scanning tests
    • Your overall physical condition must be good enough to perform daily activities, with an ECOG score of 0-2 (a scale that measures how well you can perform daily activities)
    • You can be either male or female
    • You must be an adult (18 years or older)

Who cannot join the trial?

13 criteria

  • Patients who have not been diagnosed with metastatic breast cancer (cancer that has spread beyond the breast)
  • Individuals under 18 years of age
  • Patients who have had previous treatment with alpelisib (a targeted cancer therapy)
  • Patients with untreated or active brain metastases (cancer that has spread to the brain)
  • Individuals with severe heart conditions or uncontrolled cardiovascular disease
  • Patients with uncontrolled diabetes mellitus (high blood sugar levels)
  • Those with serious active infections
  • Patients participating in other clinical trials
  • Individuals with known allergies to the study medications
  • Patients with severely impaired liver or kidney function
  • Pregnant or breastfeeding women
  • Patients unable to swallow oral medications
  • Individuals with conditions that would interfere with study participation or evaluation
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Investigated drugs

  • Inavolisib

    is a new investigational medication that targets specific mutations in breast cancer cells. It belongs to a class of drugs that work by blocking certain proteins involved in cancer cell growth. It is given in combination with fulvestrant to treat advanced breast cancer.

  • Fulvestrant

    is a hormone therapy medication that blocks the effects of estrogen on cancer cells. It is commonly used to treat hormone receptor-positive breast cancer in postmenopausal women whose disease has progressed after other hormone treatments.

  • Alpelisib

    is a targeted therapy medication that blocks specific proteins involved in cancer cell growth. Like inavolisib, it is used in combination with fulvestrant to treat certain types of advanced breast cancer that have specific genetic mutations.

  • CDK4/6 inhibitors

    are a class of medications that work by blocking specific proteins involved in cell division. These medications are typically used in combination with hormone therapy to treat hormone receptor-positive breast cancer.

What is already known about the treatment

  • Inavolisib

    An investigational oral medication being studied for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with PIK3CA mutations. It works by selectively inhibiting the PI3K pathway, which is often overactive in breast cancer cells, helping to slow down or stop cancer growth. This targeted therapy is currently being evaluated in Phase III clinical trials in combination with fulvestrant for patients who have progressed after CDK4/6 inhibitor and endocrine therapy.

  • Alpelisib

    An FDA-approved oral medication used in combination with fulvestrant for treating hormone receptor-positive, HER2-negative metastatic breast cancer with PIK3CA mutations. It functions as a PI3K inhibitor, specifically targeting the alpha form of PI3K, which plays a crucial role in cancer cell growth and survival. This targeted therapy is administered daily and has shown effectiveness in patients whose disease has progressed following endocrine therapy.

  • Fulvestrant

    An injectable hormone therapy medication that works as a selective estrogen receptor degrader (SERD) for treating hormone receptor-positive metastatic breast cancer. It is administered through intramuscular injection and works by blocking and degrading estrogen receptors in cancer cells, preventing estrogen from stimulating cancer growth. This medication is commonly used in combination with other targeted therapies for advanced breast cancer treatment.

Investigated diseases

Metastatic Breast Cancer - A form of breast cancer that has spread beyond the breast and nearby lymph nodes to other parts of the body, most commonly to the bones, liver, lungs, or brain. The cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system to form new tumors in other organs. The disease develops when breast cancer cells gain the ability to detach from the primary tumor and establish growth in distant locations. The progression of metastatic breast cancer can vary significantly among individuals. The condition is characterized by the presence of breast cancer cells in organs distant from the breast tissue.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2022-502322-41-00Protocol codeWO43919Estimated enrolment458 patientsSponsorF. Hoffmann-La Roche AG

sourced from the EU Clinical Trials Register and site verification

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