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

NCT07085767 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: OP-1250-302OPERA-02
• Study Type: interventional
• Target: 1,000
• Locations: 16 countries
• Sites: 85

Brief 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.

Conditions

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

Keywords

Randomized; Multicenter; Double-Blind; Active-Controlled; Phase 3; Palazestrant; Complete Estrogen Receptor Antagonist (CERAN); Selective Estrogen Receptor Degrader (SERD); Ribociclib; CDK4/6i; Letrozole; Aromatase inhibitors; Antineoplastic agents

Outcome Measures

Primary Outcomes (1)

• 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.

  From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

Secondary Outcomes (11)

• Overall Survival (OS)

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

• Progression Free Survival (PFS)

  From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

• Overall response Rate (ORR)

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

• Duration of Response (DOR)

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

• Clinical Benefit Rate (CBR)

  Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)

Study Arms (2)

Palazestrant

EXPERIMENTAL

Participants will receive palazestrant, ribociclib and letrozole-matching placebo

Drug: Palazestrant; Drug: Letrozole-matching placebo; Drug: Ribociclib

Letrozole

ACTIVE COMPARATOR

Participants will receive letrozole, ribociclib and palazestrant-matching placebo

Drug: Ribociclib; Drug: Letrozole; Drug: Palazestrant matching-placebo

Interventions

Palazestrant DRUG

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

Also known as: OP-1250

Palazestrant

Ribociclib DRUG

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

Letrozole; Palazestrant

Letrozole DRUG

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

Letrozole

Letrozole-matching placebo DRUG

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

Palazestrant

Palazestrant matching-placebo DRUG

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

Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Olema Pharmaceuticals, Inc.: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (85)

Clinical Trial Site

Hot Springs, Arkansas, 71913, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Santa Barbara, California, 93105, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Denver, Colorado, 80220, United States

RECRUITING

Clinical Trial Site

Peoria, Illinois, 61615, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Ames, Iowa, 50010, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Scarborough, Maine, 04074, United States

RECRUITING

Clinical Trial Site

Annapolis, Maryland, 21401, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Kansas City, Missouri, 64132, United States

RECRUITING

Clinical Trial Site

Santa Fe, New Mexico, 87505, United States

RECRUITING

Clinical Trial Site

Columbus, Ohio, 43219, United States

RECRUITING

Clinical Trial Site

Horsham, Pennsylvania, 19044, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Sayre, Pennsylvania, 18840, United States

RECRUITING

Clinical Trial Site

Knoxville, Tennessee, 37909, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Tennessee City, Tennessee, 37203, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Denton, Texas, 76201, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

El Paso, Texas, 79902, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Houston, Texas, 77024, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

San Antonio, Texas, 78229, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Salt Lake City, Utah, 84106, United States

NOT YET RECRUITING

Clinical Trial Site

Olympia, Washington, 98502, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Vancouver, Washington, 98684, United States

ACTIVE NOT RECRUITING

Clinical Trial Site

Sydney, New South Wales, 2109, Australia

RECRUITING

Clinical Trial Site

Waratah, New South Wales, 2298, Australia

RECRUITING

Clinical Trial Site

South Brisbane, Queensland, 4101, Australia

ACTIVE NOT RECRUITING

Clinical Trial Site

Adelaide, South Australia, 5000, Australia

RECRUITING

Clinical Trial Site

Clayton, Victoria, 3168, Australia

RECRUITING

Clinical Trial Site

Geelong, Victoria, 3220, Australia

RECRUITING

Clinical Trial Site

Heidelberg, Victoria, 03084, Australia

RECRUITING

Clinical Trial Site

Nedlands, Western Australia, 6009, Australia

RECRUITING

Clinical Trial Site

Toronto, Ontario, M2J 1V1, Canada

RECRUITING

Clinical Trial Site

Bobigny, 93000, France

ACTIVE NOT RECRUITING

Clinical Trial Site

Athens, Pireas, 18547, Greece

ACTIVE NOT RECRUITING

Clinical Trial Site

Thessaloniki, Thessaloniki, 57001, Greece

ACTIVE NOT RECRUITING

Clinical Trial Site

Hong Kong, Hong Kong, 999077, Hong Kong

ACTIVE NOT RECRUITING

Clinical Trial Site

Hong Kong, Kowloon, 999077, Hong Kong

RECRUITING

Clinical Trial Site

Hong Kong, Pok Fu Lam, 999077, Hong Kong

RECRUITING

Clinical Trial Site

Milan, Milano, 20132, Italy

ACTIVE NOT RECRUITING

Clinical Trial Site

Ipoh, Ipoh Perak, 30450, Malaysia

ACTIVE NOT RECRUITING

Clinical Trial Site

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

ACTIVE NOT RECRUITING

Clinical Trial Site

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

ACTIVE NOT RECRUITING

Clinical Trial Site

George Town, Pulau Pinang, 10450, Malaysia

RECRUITING

Clinical Trial Site

Kota Kinabalu, Sabah, 88996, Malaysia

RECRUITING

Clinical Trial Site

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Clinical Trial Site

Petaling Jaya, Selangor, 46050, Malaysia

ACTIVE NOT RECRUITING

Clinical Trial Site

Putrajaya, Wilayah PE, 62250, Malaysia

RECRUITING

Clinical Trial Site

Apeldoorn, Gelderland, 7334 DZ, Netherlands

ACTIVE NOT RECRUITING

Clinical Trial Site

Rzeszów, Podkarpackie Voivodeship, 35-055, Poland

ACTIVE NOT RECRUITING

Clinical Trial Site

Rzeszów, Podkarpackie Voivodeship, 35-922, Poland

ACTIVE NOT RECRUITING

Clinical Trial Site

Brzozów, Woj Podkarpackie, 36-200, Poland

ACTIVE NOT RECRUITING

Clinical Trial Site

Cluj-Napoca, Cluj, 400641, Romania

RECRUITING

Clinical Trial Site

Iași, Iaşi, 700106, Romania

ACTIVE NOT RECRUITING

Clinical Trial Site

Timișoara, Timiș County, 300239, Romania

ACTIVE NOT RECRUITING

Clinical Trial Site

Busan, Busan Metropolitan City, 49201, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Daegu, Daegu Metropolitan City, 41404, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Goyang-si, Gyeonggi-do, 10408, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Seongnam-si, Gyeonggi-do, 13620, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Clinical Trial Site

Yongin-si, Gyeonggi-do, 16499, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Seoul, Seoul, 02841, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Seoul, Seoul, 03080, South Korea

RECRUITING

Clinical Trial Site

Seoul, Seoul, 03722, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Seoul, Seoul Special City, 05505, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Seoul, Seoul Special City, 08308, South Korea

ACTIVE NOT RECRUITING

Clinical Trial Site

Alicante, Alicante, 3010, Spain

ACTIVE NOT RECRUITING

Clinical Trial Site

Barcelona, Barcelona, 08028, Spain

RECRUITING

Clinical Trial Site

Barcelona, Barcelona, 08036, Spain

ACTIVE NOT RECRUITING

Clinical Trial Site

Granada, Granada, 18012, Spain

ACTIVE NOT RECRUITING

Clinical Trial Site

Madrid, Madrid, 28040, Spain

RECRUITING

Clinical Trial Site

Murcia, Murcia, 30120, Spain

ACTIVE NOT RECRUITING

Clinical Trial Site

Valencia, Valencia, 46010, Spain

ACTIVE NOT RECRUITING

Clinical Trial Site

Chang-hua, Chang Hua, 50006, Taiwan

ACTIVE NOT RECRUITING

Clinical Trial Site

Kaohsiung City, Sanmin, 80756, Taiwan

RECRUITING

Clinical Trial Site

Taipei, Special Municipality, 11217, Taiwan

RECRUITING

Clinical Trial Site

Taipei, Special Municipality, 11490, Taiwan

ACTIVE NOT RECRUITING

Clinical Trial Site

Taipei, Taipei City, 100, Taiwan

ACTIVE NOT RECRUITING

Clinical Trial Site

Taipei, Taipei City, 10449, Taiwan

ACTIVE NOT RECRUITING

Clinical Trial Site

Bangkok, Bangkok, 10700, Thailand

RECRUITING

Clinical Trial Site

Dusit, Bangkok, 10300, Thailand

RECRUITING

Clinical Trial Site

Ban Phaeo, Changwat Samut Sakhon, 74120, Thailand

RECRUITING

Clinical Trial Site

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

Clinical Trial Site

Chiang Mai, Chiang Mai, 50200, Thailand

RECRUITING

Clinical Trial Site

Brighton, England, BN2 5BE, United Kingdom

RECRUITING

Clinical Trial Site

London, England, WC1E 6AG, United Kingdom

ACTIVE NOT RECRUITING

Clinical Trial Site

London, Greater London, EC1M 6BQ, United Kingdom

ACTIVE NOT RECRUITING

Clinical Trial Site

Guildford, Surrey, GU2 7XX, United Kingdom

ACTIVE NOT RECRUITING

Related Links

• Olema Publications

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director, MD

  Olema Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

Olema Pharmaceuticals, Inc.

CONTACT

415-651-7206; OPERA-02@olema.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 25, 2025
• Study Start: November 3, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (21); GB (4); NL (1); KR (11); MY (8); AU (8); TW (6); TH (5); FR (1); GR (2); HK (3); PL (3); ES (7); IT (1); RO (3)