Recruiting
Phase 3

Palazestrant vs. Letrozole

Sponsor:

Olema Pharmaceuticals, Inc.

Code:

NCT07085767

Conditions

Breast Cancer

Locally Advanced Breast Cancer

Metastatic Breast Cancer

ER Positive Breast Cancer

HER2 Negative Breast Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Palazestrant

Letrozole-matching placebo

Ribociclib

Letrozole

Palazestrant matching-placebo

Study Details

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

Breast Cancer

Locally Advanced Breast Cancer

Metastatic Breast Cancer

ER Positive Breast Cancer

HER2 Negative Breast Carcinoma

Study ID

NCT07085767

Start date

Nov 3, 2025

Status verified date

Sep, 2026

Completion date

Jan, 2032

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

1000 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Palazestrant

Participants will receive palazestrant, ribociclib and letrozole-matching placebo

active comparator: Letrozole

Participants will receive letrozole, ribociclib and palazestrant-matching placebo

Interventions

Palazestrant

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

Letrozole-matching placebo

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

Ribociclib

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

Letrozole

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

Palazestrant matching-placebo

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

Primary outcome measure

  • 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) ]

Central Contacts and Locations

Central contacts

Olema Pharmaceuticals, Inc.

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

Locations

Clinical Trial Site

Recruiting

Hot Springs, Arkansas, United States, 71913

Clinical Trial Site

Recruiting

Beverly Hills, California, United States, 90211

Clinical Trial Site

Recruiting

La Jolla, California, United States, 92093

Clinical Trial Site

Recruiting

Los Alamitos, California, United States, 90720

Clinical Trial Site

Recruiting

Oakland, California, United States, 94611

Clinical Trial Site

Recruiting

Roseville, California, United States, 95661

Clinical Trial Site

Recruiting

San Francisco, California, United States, 94115

Clinical Trial Site

Recruiting

San Francisco, California, United States, 94158

Clinical Trial Site

Recruiting

Santa Barbara, California, United States, 93105

Clinical Trial Site

Recruiting

Santa Clara, California, United States, 95051

Clinical Trial Site

Recruiting

Vallejo, California, United States, 94589

Clinical Trial Site

Recruiting

Walnut Creek, California, United States, 94596

Clinical Trial Site

Recruiting

Aurora, Colorado, United States, 80045

Clinical Trial Site

Recruiting

Denver, Colorado, United States, 80220

Clinical Trial Site

Recruiting

New Haven, Connecticut, United States, 06511

Clinical Trial Site

Recruiting

Tampa, Florida, United States, 33612

Clinical Trial Site

Recruiting

Marietta, Georgia, United States, 30060

Clinical Trial Site

Recruiting

Honolulu, Hawaii, United States, 96813

Clinical Trial Site

Recruiting

Peoria, Illinois, United States, 61615

Clinical Trial Site

Recruiting

Urbana, Illinois, United States, 61801

Clinical Trial Site

Recruiting

Scarborough, Maine, United States, 04074

Clinical Trial Site

Recruiting

Annapolis, Maryland, United States, 21401

Clinical Trial Site

Recruiting

Baltimore, Maryland, United States, 21201

Clinical Trial Site

Recruiting

Baltimore, Maryland, United States, 21205

Clinical Trial Site

Recruiting

Catonsville, Maryland, United States, 21228

Clinical Trial Site

Recruiting

Burlington, Massachusetts, United States, 01805

Clinical Trial Site

Recruiting

Ann Arbor, Michigan, United States, 48109

Clinical Trial Site

Recruiting

Minneapolis, Minnesota, United States, 55404

Clinical Trial Site

Recruiting

Jackson, Mississippi, United States, 39216

Clinical Trial Site

Recruiting

Kansas City, Missouri, United States, 64132

Clinical Trial Site

Recruiting

Lebanon, New Hampshire, United States, 03756

Clinical Trial Site

Recruiting

Santa Fe, New Mexico, United States, 87505

Clinical Trial Site

Recruiting

New York, New York, United States, 10029

Clinical Trial Site

Recruiting

New York, New York, United States, 10032

Clinical Trial Site

Recruiting

Charlotte, North Carolina, United States, 28204

Clinical Trial Site

Recruiting

Durham, North Carolina, United States, 27710

Clinical Trial Site

Recruiting

Cincinnati, Ohio, United States, 45245

Clinical Trial Site

Recruiting

Columbus, Ohio, United States, 43212

Clinical Trial Site

Recruiting

Columbus, Ohio, United States, 43219

Clinical Trial Site

Recruiting

Portland, Oregon, United States, 97239

Clinical Trial Site

Recruiting

Horsham, Pennsylvania, United States, 19044

Clinical Trial Site

Recruiting

Sayre, Pennsylvania, United States, 18840

Clinical Trial Site

Recruiting

Bartlett, Tennessee, United States, 38133

Clinical Trial Site

Recruiting

Knoxville, Tennessee, United States, 37909

Clinical Trial Site

Recruiting

Mount Juliet, Tennessee, United States, 37122

Clinical Trial Site

Recruiting

Nashville, Tennessee, United States, 37232

Clinical Trial Site

Recruiting

Tennessee City, Tennessee, United States, 37203

Clinical Trial Site

Recruiting

Dallas, Texas, United States, 75235

Clinical Trial Site

Recruiting

Dallas, Texas, United States, 75390

Clinical Trial Site

Recruiting

Denton, Texas, United States, 76201

Clinical Trial Site

Recruiting

El Paso, Texas, United States, 79902

Clinical Trial Site

Recruiting

Houston, Texas, United States, 77024

Clinical Trial Site

Recruiting

San Antonio, Texas, United States, 78229

Clinical Trial Site

Recruiting

Salt Lake City, Utah, United States, 84106

Clinical Trial Site

Recruiting

Fort Belvoir, Virginia, United States, 22060

Clinical Trial Site

Recruiting

Midlothian, Virginia, United States, 23114

Clinical Trial Site

Recruiting

Norfolk, Virginia, United States, 23502

Clinical Trial Site

Recruiting

Olympia, Washington, United States, 98502

Clinical Trial Site

Recruiting

Seattle, Washington, United States, 98109

Clinical Trial Site

Recruiting

Vancouver, Washington, United States, 98684

Clinical Trial Site

Recruiting

Milwaukee, Wisconsin, United States, 52336

Clinical Trial Site

Recruiting

Toronto, Ontario, Canada, M2J 1V1

Clinical Trial Site

Recruiting

Greenfield Park, Quebec, Canada, J4V 2H1

More Information

Sponsor

Olema Pharmaceuticals, Inc.

Last update posted

Sep 23, 2026

Last verified

Sep, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Olema Pharmaceuticals, Inc. on 2026-09-23. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.