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Study of BGB-43395 with letrozole versus CDK4/6 inhibitor drug combination with letrozole in patients with untreated advanced HR‑positive HER2‑negative breast cancer

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What is this trial about?

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

The trial involves patients with Advanced or Metastatic HR+/HER2- Breast Cancer, a type of breast cancer that has spread beyond the original site and shows specific hormone‑related characteristics. The study compares a new oral medicine called BGB-43395 taken together with the hormone‑blocking pill letrozole against three existing oral medicines that belong to a class known as CDK4/6 inhibitors: abemaciclib, palbociclib and ribociclib, each also combined with letrozole. The purpose of the study is to find out which treatment keeps the cancer from growing for a longer time without worsening.

This is an open‑label, phase 3 study, meaning that both doctors and participants know which medicines are being given and the research is at an advanced stage. After giving informed consent, participants are randomly assigned—by chance—to receive either the new combination or one of the standard combinations, and they take the pills daily. Throughout the study, participants have regular doctor visits and simple scans to check the size of the cancer, and they report any side effects, while the overall health and quality of life are also monitored over several months.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization and assignment to treatment arm

    After joining the study you will be randomly placed in one of two groups. one group receives bgb-43395 plus letrozole; the other group receives a CDK4/6 inhibitor (abemaciclib, palbociclib or ribociclib) plus letrozole. the assignment is made by the study team and you will be informed which medicines you will take.

  2. Step 2

    Baseline examinations

    Before starting medication you will have a physical check‑up, blood tests, and imaging scans (such as ct or mri) to record the current status of the cancer. these results are used as a reference for later comparisons.

  3. Step 3

    Start of study medication

    If you are in the bgb-43395 plus letrozole group, you will take letrozole 2.5 mg by mouth once each day and bgb-43395 at the dose prescribed by the investigator, also taken by mouth once each day.

    If you are in the CDK4/6 inhibitor plus letrozole group, you will take letrozole 2.5 mg by mouth once each day and one of the following:

    abemaciclib 300 mg by mouth once each day,

    palbociclib 125 mg by mouth once each day for three weeks followed by one week without the drug (a 28‑day cycle),

    ribociclib 600 mg by mouth once each day for three weeks followed by one week without the drug (a 28‑day cycle).

  4. Step 4

    Regular safety visits

    You will visit the clinic roughly every four weeks. during these visits blood tests and a review of any side effects will be performed to ensure the medication is tolerated.

  5. Step 5

    Tumor assessments

    Imaging scans to evaluate the tumor will be done about every eight weeks. the scans are compared with the baseline images to determine whether the disease is stable, improving, or progressing.

  6. Step 6

    Continuation of treatment

    You will keep taking the assigned medicines daily (or according to the 3‑weeks‑on, 1‑week‑off schedule for palbociclib or ribociclib) until one of the following occurs:

    The cancer shows progression on imaging,

    Unacceptable side effects develop,

    The investigator decides to stop treatment for any reason,

    Or the study reaches its planned end.

  7. Step 7

    End‑of‑treatment evaluation

    When treatment stops, a final set of assessments will be performed, including physical exam, blood tests, and imaging, to record the condition of the disease at the time of discontinuation.

Who can join the trial?

4 criteria

  • You are at least 18 years old (or the legal age to give consent in your country) when you sign the study agreement.
  • You have breast cancer that has been confirmed by a lab test of tissue (histologically confirmed) and is either locally advanced or has spread to other parts of the body (metastatic), and it is a type that is hormone‑receptor positive (HR+) and HER2‑negative (HER2‑).
  • You have a stable ECOG Performance Status of 0 or 1, meaning you are fully active or can do light work but not strenuous activity.
  • Your main organs (such as liver, kidneys, and bone marrow) are working well enough (adequate organ function) for the study treatments.

Who cannot join the trial?

3 criteria

  • People who have already received systemic treatment—therapy that travels through the bloodstream to treat cancer throughout the body—in the advanced or metastatic stage cannot take part.
  • People who have previously taken any selective cyclin‑dependent kinase 4 (CDK4) or cyclin‑dependent kinase 2 (CDK2) targeting drugs, or any other investigational anticancer drug—a cancer medicine that is still being tested and not yet approved—are not eligible.
  • People with active leptomeningeal disease—cancer that has spread to the thin membranes covering the brain and spinal cord—or with uncontrolled, untreated brain metastasis—cancer spots in the brain that have not been treated or are not under control—cannot join the study.
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Investigated drugs

  • Letrozole

    is a pill taken by mouth that lowers the amount of estrogen the body makes. In this study it is given together with other drugs to help slow the growth of hormone‑sensitive breast cancer that has spread or come back.

  • BGB-43395

    is an experimental oral medication that works by blocking proteins called CDK4 and CDK6, which cancer cells need to grow and divide. In the trial it is tested in combination with letrozole to see if it can keep the cancer from getting worse for a longer time.

  • Abemaciclib

    is a tablet taken by mouth that also blocks CDK4 and CDK6 enzymes. It is already used for treating advanced hormone‑positive breast cancer. In this study it is combined with letrozole to compare its effectiveness with the new drug BGB-43395.

  • Palbociclib

    is an oral tablet that inhibits CDK4 and CDK6, helping to stop cancer cells from multiplying. In the trial it is given together with letrozole, and its results are compared with those of BGB-43395 plus letrozole.

  • Ribociclib

    is a pill taken by mouth that blocks the same CDK4/6 enzymes, slowing the growth of breast cancer cells. In this study it is used with letrozole as another comparison group against the experimental BGB-43395 plus letrozole regimen.

What is already known about the treatment

  • Letrozole

    Letrozole is taken by mouth as a tablet. It is an approved medication that is widely used for hormone‑dependent breast cancer. It works by blocking the enzyme aromatase, which reduces estrogen levels that can help tumors grow. It belongs to the class of aromatase inhibitors.

  • Palbociclib

    Palbociclib is taken by mouth as a tablet. It is an approved drug for treating advanced hormone‑positive, HER2‑negative breast cancer. It blocks the proteins CDK4 and CDK6, stopping cancer cells from dividing and growing. It is classified as a selective CDK4/6 inhibitor.

  • Ribociclib

    Ribociclib is taken orally as a tablet. It is approved for use in advanced hormone‑positive, HER2‑negative breast cancer. It inhibits CDK4 and CDK6 enzymes, which are needed for cancer cells to progress through the cell cycle. It is a selective CDK4/6 inhibitor.

  • Abemaciclib

    Abemaciclib is taken by mouth as a tablet. It is an approved therapy for advanced hormone‑positive, HER2‑negative breast cancer. It works by blocking CDK4 and CDK6, preventing cancer cells from multiplying. It is also a selective CDK4/6 inhibitor.

  • BGB‑43395

    BGB‑43395 is taken orally as a film‑coated tablet. It is currently an investigational drug being studied in clinical trials for advanced hormone‑positive, HER2‑negative breast cancer. It acts by inhibiting the CDK4 and CDK6 proteins, which stops tumor cells from dividing. It is classified as an experimental CDK4/6 inhibitor.

Investigated diseases

Advanced hormone receptor‑positive, HER2‑negative breast cancer - It is a type of breast cancer that expresses estrogen or progesterone receptors but lacks overexpression of the HER2 protein. It typically begins in the breast and, when advanced or metastatic, has spread beyond the breast to distant organs such as bone, liver, lung, or brain. The disease grows by cell division driven by hormones, leading to tumor enlargement and formation of new lesions. Metastatic spread occurs through blood or lymphatic vessels, allowing cancer cells to implant in other tissues. Over time, tumors may increase in size and number, causing symptoms related to the involved organs. The condition is monitored by imaging and clinical assessment to track disease changes.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-523960-19-00Protocol codeBGB-43395-302Estimated enrolment1 056 patientsSponsorBeOne Medicines I GmbH

sourced from the EU Clinical Trials Register and site verification

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