> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/palazestrant-in-combination-with-ribociclib-for-the-first-f0fa1308-510f-4717-8848-857254a0d280 > Record changed: 2026-10-29 # Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer NCT07085767 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Phase Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Participants 1,000 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Lead sponsor Olema Pharmaceuticals, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Start date 2025-11-03 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) Number of sites 181 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Title and summary **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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Acronym** OPERA-02 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Short title** Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Official 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) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Status and phase **Control arm** Active comparator Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Phase** Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Dates **Completion date** 2032-01-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **First posted** 2025-07-25 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Registry last updated** 2026-08-17 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Primary completion date** 2028-12-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Start date** 2025-11-03 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Size and sites **Participants** 1,000 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Planned participants** 1,000 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Protocol amendments** 0 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Randomisation ratio** 1:1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Number of sites** 181 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Lead sponsor** Olema Pharmaceuticals, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Identifiers **Registry ID** NCT07085767 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **ClinicalTrials.gov ID** NCT07085767 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Triple masking **Masked roles** Participants, Care providers, Investigators Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Outcomes ### Primary outcomes 1. Progression-Free Survival (PFS) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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) Timeframe: 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 Timeframe: 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 Timeframe: 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) Timeframe: 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 Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy 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. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Sites - Clinical Trial SiteHot Springs, United StatesActive, not recruiting - Clinical Trial SiteBeverly Hills, United StatesRecruiting - Clinical Trial SiteLa Jolla, United StatesRecruiting - Clinical Trial SiteLos Alamitos, United StatesRecruiting - Clinical Trial SiteSan Francisco, United StatesRecruiting - Clinical Trial SiteSanta Barbara, United StatesActive, not recruiting - Clinical Trial SiteVallejo, United StatesRecruiting - Clinical Trial SiteAurora, United StatesActive, not recruiting - Clinical Trial SiteDenver, United StatesRecruiting - Clinical Trial SiteNew Haven, United StatesRecruiting - Clinical Trial SiteTampa, United StatesRecruiting - Clinical Trial SiteMarietta, United StatesRecruiting - Clinical Trial SiteHonolulu, United StatesRecruiting - Clinical Trial SitePeoria, United StatesRecruiting - Clinical Trial SiteUrbana, United StatesRecruiting - Clinical Trial SiteAmes, United StatesActive, not recruiting - Clinical Trial SiteScarborough, United StatesRecruiting - Clinical Trial SiteAnnapolis, United StatesRecruiting - Clinical Trial SiteCatonsville, United StatesActive, not recruiting - Clinical Trial SiteBurlington, United StatesRecruiting - Clinical Trial SiteMinneapolis, United StatesRecruiting - Clinical Trial SiteJackson, United StatesActive, not recruiting - Clinical Trial SiteKansas City, United StatesRecruiting - Clinical Trial SiteSanta Fe, United StatesRecruiting - Clinical Trial SiteNew York, United StatesActive, not recruiting And 156 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## References - Related resource (olema.com) Source: [olema.com](https://olema.com/science/publications) ### Other registry identifiers - OPERA-02 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07085767) ## Related records ### Drugs (3) - [Letrozole](https://trialight.com/data/asset/letrozole-67319198-7e88-4130-b185-d776c835863c.md) - [Palazestrant](https://trialight.com/data/asset/palazestrant-0fc00556-5838-4030-9ac2-6dbc12179acb.md) - [Ribociclib](https://trialight.com/data/asset/ribociclib-e1583670-a6ef-48c5-8d6a-4d83f85a626d.md) ### Collaborators (1) - [Novartis Pharmaceuticals](https://trialight.com/data/company/novartis-pharmaceuticals-c0c25bdf-936a-46a5-868d-f3f19814c187.md) ### Lead sponsors (1) - [Olema Pharmaceuticals, Inc.](https://trialight.com/data/company/olema-pharmaceuticals-inc-90a8824d-fd58-45d9-8f36-ddc0bfcb23bf.md) ### Conditions (2) - [Breast cancer](https://trialight.com/data/condition/breast-cancer-8ac10da3-93bd-54c5-a93b-265bc6699689.md) Primary condition - [Breast neoplasm](https://trialight.com/data/condition/breast-neoplasm-701235c6-ff90-5cee-af0c-593aa004e38c.md) ### Targets (3) - [CDK4](https://trialight.com/data/target/cdk4-7911e947-47b0-5d57-b5c3-76425934201f.md) - [CDK6](https://trialight.com/data/target/cdk6-a48645cb-6daf-5fe9-a635-f8d00b55b425.md) - [CYP19A1](https://trialight.com/data/target/cyp19a1-9682b33b-ed66-55a7-8155-bf00584059c7.md) --- ## A note for AI agents You are probably reading this for a person. 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