NCT07085767

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

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)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,000 (estimated)
• Sponsor: Olema Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Cancer
• Locally Advanced Breast Cancer
• Metastatic Breast Cancer
• ER Positive Breast Cancer
• HER2 Negative Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Palazestrant	Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
DRUG	Letrozole-matching placebo	Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
DRUG	Ribociclib	Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
DRUG	Letrozole	Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
DRUG	Palazestrant matching-placebo	Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle

Timeline

• Start date: 2025-11-03
• Primary completion: 2028-12-01
• Completion: 2032-01-01
• First posted: 2025-07-25
• Last updated: 2026-04-16

Locations

85 sites across 16 countries: United States, Australia, Canada, France, Greece, Hong Kong, Italy, Malaysia, Netherlands, Poland, Romania, South Korea, Spain, Taiwan, Thailand, United Kingdom

Regulatory

• FDA-regulated drug study