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RecruitingLast updated: 2 April 2026

OPERA-02: Comparing combinations of targeted therapy and hormone therapy in people with ER+, HER2- advanced breast cancer who haven't had prior systemic treatment for their advanced disease.A Phase 3 Randomized, Double-Blind, Active-Controlled Study of Palazestrant With Ribociclib Versus Letrozole With Ribociclib for the First-Line Treatment of ER+, HER2- Advanced Breast Cancer (OPERA-02)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Breast Cancers Breast

Age

People18+

Trial acronym

OPERA-02

Clinical summary

Summary

The purpose of this trial is to compare how safe and effective palazestrant is in combination with ribociclib and a placebo that matches letrozole, versus letrozole, ribociclib and a placebo that matches palazestrant. 

Palazestrant is a targeted hormone therapy, ribociclib is a targeted therapy and letrozole is a hormone therapy.

This trial is seeking adults with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for their advanced disease.

Eligible participants will be randomly allocated (by chance) to one of two treatment arms.

In the Experimental Arm, participants will receive palazestrant once daily

will receive palazestrant once daily on a 4-week cycle, plus ribociclib once daily on Days 1-21 of a 4 week cycle, and a placebo that matches letrozole once daily on a 4-week cycle.

In the Active Comparator Arm, participants will receive letrozole once daily on a 4 week cycle, plus ribociclib once daily on Days 1-21 of a 4 week cycle, and a placebo that matches palazestrant once daily on a 4 week cycle.

Conditions

This trial is treating people with locally advanced or metastatic breast cancer that is ER+ and HER-

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 per RECIST 1.1 or bone-only disease).
  • De novo advanced breast cancer or with disease recurrence occurring after 12 months of completing adjuvant endocrine therapy (with or without CDK4/6 inhibitors)
  • 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

  • Disease recurrence during adjuvant endocrine therapy
  • Currently receiving or previously received systemic anti-cancer therapy for ER+, HER2- advanced breast cancer.
  • Previously received treatment with fulvestrant, elacestrant or an investigational endocrine therapy in any setting.
  • History of allergic reactions to study treatment.
  • Any contraindications to letrozole and ribociclib.
  • Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You are able to swallow medication by mouth.

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.

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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, Double-Blind, Active-Controlled Study of Palazestrant With Ribociclib Versus Letrozole With Ribociclib for the First-Line Treatment of ER+, HER2- Advanced Breast Cancer (OPERA-02)

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