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RecruitingLast updated: 13 July 2026

OPERA-01: Comparing the safety and effectiveness of a new hormone medicine (called palazestrant) to standard treatments for people with ER+, HER2- advanced or metastatic breast cancerA Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy

Trial purpose

Medical clipboardCancer treatment

Tumor type

Breast Cancers Breast

Age

People18+

Trial acronym

OPERA-01

Clinical summary

Summary

This clinical trial is testing a new hormone therapy medicine called palazestrant (also known as OP-1250) for people with advanced breast cancer. 

The trial is comparing palazestrant with standard hormone treatments, including fulvestrant and aromatase inhibitors (anastrozole, letrozole, or exemestane). The aim is to find out how well palazestrant works compared to standard treatments, how safe it is, and what side effects it causes.

Who is this trial for?
You may be eligible if:

  • You have advanced breast cancer that has spread (metastatic) or cannot be cured with surgery (unresectable)
  • Your cancer is hormone receptor-positive (ER+) and HER2-negative
  • Your cancer has already been treated with hormone therapy and a CDK4/6 inhibitor
  • Your cancer has come back or gotten worse after this treatment

What the trial involves
The study is carried out in two stages:

In the first stage, about 120 people will be assigned to receive one of two different doses of palazestrant, or a standard hormone treatment. This helps researchers work out which dose of palazestrant is the most suitable.

In the second stage, around 390 more people will join the trial. They will receive either palazestrant at the chosen dose or a standard hormone treatment.

In both stages, the type of treatment each person receices will be decided randomly (by chance). 

 

Conditions

This trial is treating people with ER+, HER2- locally advanced or metastatic breast cancer whose disease has advanced after receiving at least one hormone therapy in combination with a CDK4/6 inhibitor

Eligibility

Inclusion

  • Adult female or male participants.
  • ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.
  • Evaluable disease (measurable disease or bone-only disease).
  • Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy is allowed. Duration of the most recent prior ET must be at least 6 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate hematologic, hepatic, and renal functions.
  • Female participants can be pre-, peri- or postmenopausal.
  • Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.

Exclusion

  • Symptomatic visceral disease, imminent organ failure, or any other reason that makes the participant ineligible for endocrine monotherapy.
  • Previously received chemotherapy in the advanced/metastatic setting.
  • Previously received treatment with elacestrant or an investigational estrogen receptor-directed therapy.
  • History of allergic reactions to study treatment.
  • Any contraindications to the selected standard-of-care endocrine therapy in the local prescribing information.
  • Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.
  • Clinically significant comorbidities such as significant cardiac or cerebrovascular disease, gastrointestinal disorders that could affect absorption of study treatment.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body, but it is not possible to perform surgery to remove it (unresectable).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Olema Pharmaceuticals, Inc.

Scientific Title

A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy

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