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)
Olema Pharmaceuticals, Inc.
1,000 participants
Nov 3, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria8
- 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 Criteria6
- 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.
Interventions
Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle
Locations(35)
View Full Details on ClinicalTrials.gov
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NCT07085767