RecruitingInterventionalPhase 3

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)

NCT ID: NCT07085767Sponsor: Olema Pharmaceuticals, Inc.Last updated: 2026-06-16

Summary

This phase 3 clinical trial compares the efficacy and safety of palazestrant with ribociclib to letrozole and ribociclib in women and men who have not received prior systemic anti-cancer treatment for advanced breast cancer.

Detailed description

This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm). This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.

Arms & interventions

DrugPalazestrant
Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
DrugLetrozole-matching placebo
Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
DrugRibociclib
Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
DrugLetrozole
Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
DrugPalazestrant matching-placebo
Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle

Outcome measures

Primary

Progression-Free Survival (PFS)
To compare PFS, based on a local investigator assessment, between investigational (palazestrant with ribociclib + letrozole-matching placebo) and control (letrozole with ribociclib + palazestrant-matching placebo) arms.
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

Secondary

Overall Survival (OS)
Time frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)
Progression Free Survival (PFS)
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)
Overall response Rate (ORR)
Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)
Duration of Response (DOR)
Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)
Clinical Benefit Rate (CBR)
Time frame: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)
Overall response Rate (ORR)
Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)
Duration of Response (DOR)
Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)
Clinical Benefit Rate (CBR)
Time frame: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)
Safety and tolerability
Time frame: Up to 42 days after end of treatment (estimated as up to 3.5 years)
Pharmacokinetics (PK) of palazestrant and ribociclib
Time frame: Every 28 days (estimated as up to 3.5 years)
Health-related patient-reported outcomes (PROs)
Time frame: Every 28 days (estimated as up to 3.5 years)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * 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 Criteria: * 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.

Study locations (37)

Clinical Trial Site

Hot Springs, Arkansas, 71913

Active Not Recruiting

Clinical Trial Site

Beverly Hills, California, 90211

Active Not Recruiting

Clinical Trial Site

San Francisco, California, 94115

Active Not Recruiting

Clinical Trial Site

Santa Barbara, California, 93105

Active Not Recruiting

Clinical Trial Site

Aurora, Colorado, 80045

Active Not Recruiting

Clinical Trial Site

Denver, Colorado, 80220

Recruiting

Clinical Trial Site

New Haven, Connecticut, 06511

Active Not Recruiting

Clinical Trial Site

Tampa, Florida, 33612

Active Not Recruiting

Clinical Trial Site

Marietta, Georgia, 30060

Recruiting

Clinical Trial Site

Honolulu, Hawaii, 96813

Active Not Recruiting

Clinical Trial Site

Peoria, Illinois, 61615

Recruiting

Clinical Trial Site

Urbana, Illinois, 61801

Active Not Recruiting

Clinical Trial Site

Ames, Iowa, 50010

Active Not Recruiting

Clinical Trial Site

Scarborough, Maine, 04074

Recruiting

Clinical Trial Site

Annapolis, Maryland, 21401

Recruiting

Clinical Trial Site

Minneapolis, Minnesota, 55404

Recruiting

Clinical Trial Site

Kansas City, Missouri, 64132

Recruiting

Clinical Trial Site

Santa Fe, New Mexico, 87505

Recruiting

Clinical Trial Site

New York, New York, 10032

Active Not Recruiting

Clinical Trial Site

Charlotte, North Carolina, 28204

Active Not Recruiting

Clinical Trial Site

Cincinnati, Ohio, 45245

Recruiting

Clinical Trial Site

Columbus, Ohio, 43219

Recruiting

Clinical Trial Site

Horsham, Pennsylvania, 19044

Active Not Recruiting

Clinical Trial Site

Sayre, Pennsylvania, 18840

Recruiting

Clinical Trial Site

Bartlett, Tennessee, 38133

Active Not Recruiting

Clinical Trial Site

Knoxville, Tennessee, 37909

Active Not Recruiting

Clinical Trial Site

Mount Juliet, Tennessee, 37122

Active Not Recruiting

Clinical Trial Site

Tennessee City, Tennessee, 37203

Recruiting

Clinical Trial Site

Denton, Texas, 76201

Recruiting

Clinical Trial Site

El Paso, Texas, 79902

Recruiting

Clinical Trial Site

Houston, Texas, 77024

Recruiting

Clinical Trial Site

San Antonio, Texas, 78229

Active Not Recruiting

Clinical Trial Site

Salt Lake City, Utah, 84106

Not Yet Recruiting

Clinical Trial Site

Fort Belvoir, Virginia, 22060

Active Not Recruiting

Clinical Trial Site

Norfolk, Virginia, 23502

Active Not Recruiting

Clinical Trial Site

Olympia, Washington, 98502

Active Not Recruiting

Clinical Trial Site

Vancouver, Washington, 98684

Active Not Recruiting