A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)
Summary
This phase 3 clinical trial compares the safety and efficacy of palazestrant (OP-1250) to the standard-of-care options of fulvestrant or an aromatase inhibitor in women and men with breast cancer whose disease has advanced on one endocrine therapy in combination with a CDK4/6 inhibitor.
Detailed description
This is an international, multicenter, randomized, open-label, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the safety and efficacy of palazestrant (OP-1250) as a single agent to the standard of care endocrine therapy: either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane). This trial is seeking adult participants with ER+, HER2- advanced or metastatic breast cancer whose disease has relapsed or progressed on 1 or 2 prior lines of standard-of-care endocrine therapy for metastatic breast cancer. Prior lines of therapy must include one line of endocrine therapy in combination with a CDK 4/6 inhibitor. In the dose-selection part of the trial, approximately 120 participants will be randomized to one of the two doses of palazestrant or to the standard-of-care endocrine therapy. Thereafter, approximately 390 participants will be randomized to palazestrant at the selected dose or to the standard-of-care endocrine therapy.
Arms & interventions
- DrugPalazestrant
Participants will be treated with palazestrant once daily on a 4 week (28 day) cycle. Doses evaluated in the dose-selection part will be 120 mg once daily and 90 mg once daily.
- DrugFulvestrant
Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle
- DrugAnastrozole
Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle
- DrugLetrozole
Participants will be treated with letrozole once daily on a 4 week (28 day) cycle
- DrugExemestane
Participants will be treated with exemestane once daily on a 4 week (28 day) cycle
Outcome measures
Primary
Dose-Selection Part: Incidence of adverse events
To evaluate the number of participants with adverse events
Time frame: From Date of Randomization up to 16 weeks
Dose-Selection Part: Incidence of dose reduction
To evaluate the number of participants reducing the dose of palazestrant
Time frame: From Date of Randomization up to 16 weeks
Dose-Selection Part: Incidence of drug discontinuation
To evaluate the number of participants discontinuing palazestrant
Time frame: From Date of Randomization up to 16 weeks
Trial: Progression-Free Survival (PFS)
To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1-mutation detected and ESR1-mutation not detected participants.
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years)
Secondary
Trial: Overall Survival (OS)
Time frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years)
Eligibility criteria
Study locations (47)
Clinical Trial Site
Tucson, Arizona, 85719
Clinical Trial Site
Fountain Valley, California, 92708
Clinical Trial Site
Glendale, California, 91204
Clinical Trial Site
La Jolla, California, 92093
Clinical Trial Site
Los Alamitos, California, 90720
Clinical Trial Site
Los Angeles, California, 90027
Clinical Trial Site
Whittier, California, 90602
Clinical Trial Site
Aurora, Colorado, 80045
Clinical Trial Site
Denver, Colorado, 80218
Clinical Trial Site
Golden, Colorado, 80401
Clinical Trial Site
Grand Junction, Colorado, 81505
Clinical Trial Site
Danbury, Connecticut, 06810
Clinical Trial Site
Newark, Delaware, 19713
Clinical Trials Site
Jacksonville, Florida, 32223
Clinical Trial Site
Margate, Florida, 33063
Clinical Trial Site
Orlando, Florida, 32804
Clinical Trial Site
Plantation, Florida, 33324
Clinical Trial Site
Tamarac, Florida, 33321
Clinical Trial Site
Atlanta, Georgia, 30322
Clinical Trial Site
Chicago, Illinois, 60616-2315
Clinical Trial Site
Chicago, Illinois, 60637
Clinical Trial Site
Urbana, Illinois, 61801
Clinical Trial Site
Baton Rouge, Louisiana, 70809
Clinical Trial Site
New Orleans, Louisiana, 70112
Clinical Trial Site
Baltimore, Maryland, 21201
Clinical Trial Site
Boston, Massachusetts, 02111
Clinical Trial Site
Detroit, Michigan, 48202
Clinical Trial Site
Saint Louis Park, Minnesota, 55426
Clinical Trial Site
Woodbury, Minnesota, 55125
Clinical Trial Site
Lincoln, Nebraska, 68516
Clinical Trial Site
Farmington, New Mexico, 87401
Clinical Trial Site
New York, New York, 10032
Clinical Trial Site
Port Jefferson Station, New York, 11776
Clinical Trial Site
Dayton, Ohio, 45415
Clinical Trial Site
Toledo, Ohio, 43623
Clinical Trial Site
Portland, Oregon, 97239
Clinical Trial Site
Sayre, Pennsylvania, 18840
Clinical Trial Site
Nashville, Tennessee, 37203
Clinical Trial Site
Nashville, Tennessee, 37208
Clinical Trial Site
Nashville, Tennessee, 37232
Clinical Trial Site
Dallas, Texas, 75246
Clinical Trial Site
Dallas, Texas, 75390
Clinical Trial Site
Houston, Texas, 77054
Clinical Trial Site
Webster, Texas, 77598
Clinical Trial Site
Ogden, Utah, 84405
Clinical Trial Site
Spokane, Washington, 99204
Clinical Trial Site
Spokane, Washington, 99208
References
- Pistilli B, Bellet Ezquerra M, Del Mastro L, Sohn J, Schmid P, Meisel J, Chan A, Zheng L, de Kermadec E, McArthur H. OPERA-01: a phase III study of palazestrant for ER+, HER2- advanced breast cancer after CDK4/6 inhibitor therapy. Future Oncol. 2026 Jan;22(2):157-166. doi: 10.1080/14796694.2025.2608863. Epub 2025 Dec 29.(PubMed)