Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07085767

Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms ER Positive Breast Cancer HER2 Negative Breast Carcinoma Locally Advanced Breast Cancer Metastatic Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Clinical Trial Site, Sydney, New South Wales, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Palazestrant

Drug

Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.

Other names: OP-1250

Letrozole-matching placebo

Drug

Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle

Ribociclib

Drug

Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.

letrozole

Drug

Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle

Palazestrant matching-placebo

Drug

Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle

Primary outcomes

  1. 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)

    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.

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)

    To compare OS between investigational and control arms.

  2. 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)

    To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment

  3. Overall response Rate (ORR)

    Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)

    To evaluate ORR based on Blinded Independent Review Committee (BIRC) assessment

  4. Duration of Response (DOR)

    Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)

    To evaluate DOR based on Blinded Independent Review Committee (BIRC) assessment

  5. 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)

    To evaluate CBR based on Blinded Independent Review Committee (BIRC) assessment

  6. Overall response Rate (ORR)

    Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)

    To evaluate ORR based on local investigator assessment

  7. Duration of Response (DOR)

    Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)

    To evaluate DOR based on local investigator assessment

  8. 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)

    To evaluate CBR based on local investigator assessment

  9. Safety and tolerability

    Time frame: Up to 42 days after end of treatment (estimated as up to 3.5 years)

    To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements

  10. Pharmacokinetics (PK) of palazestrant and ribociclib

    Time frame: Every 28 days (estimated as up to 3.5 years)

    To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters

  11. Health-related patient-reported outcomes (PROs)

    Time frame: Every 28 days (estimated as up to 3.5 years)

    To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials

Study contacts

Contact information is provided by the study sponsor or research team.

Olema Pharmaceuticals, Inc.

CONTACT

[email protected]

415-651-7206

Sponsors and collaborators

Lead sponsor

Olema Pharmaceuticals, Inc.

Industry

Collaborators

  • Novartis Pharmaceuticals

Registry information

Official study 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)

Acronym: OPERA-02

Important dates

Study start
2025
Primary completion
2028
Study completion
2032
First posted
Jul 25, 2025
Registry last updated
Jul 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.