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A study of palazestrant and ribociclib compared to letrozole and ribociclib for patients with advanced ER+ HER2- breast cancer

Fast replyRegistered 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 is focused on treating Advanced Breast Cancer that is ER-positive and HER2-negative. This means the cancer cells have receptors for estrogen, a female hormone, but do not have high amounts of a specific protein that helps cancer grow. The goal of the study is to compare the effectiveness of two different treatment combinations. One group will receive palazestrant, also known as OP-1250, along with ribociclib and a gonadotropin releasing hormone analogue, which is a medication used to lower hormone levels. The other group will receive letrozole and ribociclib, along with a placebo.

Participants in the study will take these medications over a period of time to see how they affect the growth of the cancer. The study looks at progression-free survival, which is the length of time during and after treatment that a person lives with the disease without it getting worse. Other factors being observed include overall survival, which is the total length of time a person remains alive, and how well the tumor responds to the medication. The study also monitors how well the body tolerates the drugs and how they impact daily life through patient questionnaires.

The research process

The trial runs in 3 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Treatment initiation

    After joining the study, an implantation of a gonadotropin releasing hormone analogue (a medication used to reduce hormone levels) with a dose of 3.60 mg is performed.

    You will be assigned to one of two treatment groups. you will take ribociclib at a dose of 600 mg taken orally (by mouth).

  2. Step 2

    Combination therapy

    If assigned to the investigational group, you will take palazestrant at a dose of 90 mg as a film-coated tablet taken orally, along with letrozole-matching placebo tablets (tablets that look like the medication but contain no active substance).

    If assigned to the control group, you will take letrozole at a dose of 2.5 mg as a capsule taken orally, along with palazestrant-matching placebo tablets.

  3. Step 3

    Monitoring and evaluation

    During the trial, progression-free survival (the length of time during and after treatment that the disease does not get worse) is monitored by an investigator.

    plasma levels (the amount of medication in the blood) of palazestrant and ribociclib are measured at specific intervals.

    Health is monitored through safety and tolerability assessments, which include checking for adverse events (side effects), laboratory parameters (blood tests), ecgs (tests that check heart rhythm), vital signs, and performance status (a measure of daily functioning).

    Your well-being is also tracked using questionnaires to assess your quality of life.

Who can join the trial?

8 criteria

  • You must be an adult, meaning an adult female or male.
  • You must have ER+ (estrogen receptor-positive) and HER2- (human epidermal growth factor receptor 2-negative) breast cancer that is either locally advanced (meaning it has spread to nearby tissues) or metastatic (meaning it has spread to other parts of the body) and cannot be completely cured by current treatments.
  • The cancer must be evaluable, which means it can be measured using specific medical rules (called RECIST 1.1) or it is located only in the bones.
  • The cancer must be de novo (newly diagnosed at an advanced stage) or it must have returned (recurrence) at least 12 months after you finished adjuvant endocrine therapy (hormone treatment given after primary treatment to prevent cancer from coming back).
  • You must have an ECOG performance status of 0 or 1, which is a scale used by doctors to measure how well you can perform daily activities and your overall level of functioning.
  • You must have adequate hematologic, hepatic, and renal functions, which means your blood counts, liver health, and kidney health must be at safe and normal levels.
  • Female participants can be in any stage of menopause (the time in a woman's life when menstruation stops).
  • Male participants and females who have not yet gone through menopause must be willing to take a GnRH agonist, which is a type of medication used to lower hormone levels.

Who cannot join the trial?

6 criteria

  • The cancer has returned while receiving adjuvant endocrine therapy, which is hormone treatment given after primary treatment to prevent the cancer from coming back.
  • The patient is currently taking or has previously taken systemic anti-cancer therapy, which means medicines that travel through the entire body to fight cancer, specifically for ER+, HER2- advanced breast cancer.
  • The patient has previously used medications called fulvestrant, elacestrant, or any experimental hormone treatments.
  • The patient has a history of allergic reactions to the medications used in this study.
  • The patient has any medical reasons why they should not take letrozole or ribociclib.
  • The patient has cancer that has spread to the central nervous system (the brain and spinal cord) and is causing symptoms, such as carcinomatous meningitis (cancer spreading to the protective layers covering the brain and spinal cord), leptomeningeal disease (cancer in the fluid surrounding the brain and spine), or spinal cord compression (the tumor pressing on the spinal cord) that needs urgent care.
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Investigated drugs

  • Ribociclib

    is an oral medication used as part of the treatment to help slow the growth of cancer cells in patients with advanced breast cancer.

  • Palazestrant

    is an oral medication being tested in this study to help block the hormones that allow certain types of breast cancer cells to grow.

  • Letrozole

    is an oral medication used as a comparison treatment to help lower the amount of estrogen in the body, which can help stop the growth of some breast cancers.

What is already known about the treatment

  • Ribociclib

    This medication is taken by mouth as an oral treatment for advanced breast cancer. It is an established cancer drug that works by blocking specific proteins in the cell that allow cancer cells to divide and grow. Scientifically classified as a CDK4/6 inhibitor, it helps slow down the progression of the disease at a cellular level.

  • Palazestrant

    This experimental medication is administered orally in the form of a film-coated tablet for the treatment of advanced breast cancer. It belongs to a class of drugs known as selective estrogen receptor degraders, which work by attaching to and breaking down the estrogen receptors that cancer cells use to grow. By removing these receptors, the drug prevents the hormone from fueling the tumor's development.

  • Letrozole

    This medication is taken orally to help treat certain types of advanced breast cancer. It is a commonly used medicine classified as an aromatase inhibitor, which works by blocking the enzyme responsible for producing estrogen in the body. By lowering estrogen levels, it deprives cancer cells of the hormonal signals they need to multiply.

Investigated diseases

ER+, HER2- Advanced Breast Cancer - This is a type of breast cancer where the cells have receptors for estrogen and the disease has reached an advanced stage. The cancer cells grow and spread because they use estrogen to fuel their development. In this specific form, the cells do not have high levels of a protein called HER2. As the disease progresses, the cancer cells can move from the original site in the breast to other parts of the body. The growth is driven by the presence of specific hormone receptors on the surface of the cancer cells.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-522873-12-00Protocol codeOP-1250-302Estimated enrolment1 028 patientsSponsorOlema Pharmaceuticals Inc.

sourced from the EU Clinical Trials Register and site verification

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On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

This service is not affiliated with the European Commission, the EMA, or the official CTIS system. Most information comes from publicly available international clinical-trial registries, supplemented by data from academic sites, national regulators and commercial sponsors. On this site, “treatment” and “therapy” mean a medicine being tested in a clinical trial. Its safety and effectiveness in the use being studied are not yet confirmed, some participants may receive a placebo or a comparator, and taking part does not guarantee a health benefit. The doctor at the research site decides who can take part. This site provides information, not medical advice. Certain content and visual elements on this website have been generated or enhanced using artificial intelligence (AI).