NCT06016738 · Olema Pharmaceuticals, Inc.
OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer
(OPERA-01)
What this study is about
This phase 3 clinical trial compares the safety and effectiveness 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.
View original scientific description
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.
Interventions
DRUG
Palazestrant
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.
DRUG
Fulvestrant
Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle
DRUG
Anastrozole
Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle
DRUG
Letrozole
Participants will be treated with letrozole once daily on a 4 week (28 day) cycle
DRUG
Exemestane
Participants will be treated with exemestane once daily on a 4 week (28 day) cycle
Primary outcome measures
Dose-Selection Part: Incidence of adverse events
Time frame: From Date of Randomization up to 16 weeks
To evaluate the number of participants with adverse events
Dose-Selection Part: Incidence of dose reduction
Time frame: From Date of Randomization up to 16 weeks
To evaluate the number of participants reducing the dose of palazestrant
Dose-Selection Part: Incidence of drug discontinuation
Time frame: From Date of Randomization up to 16 weeks
To evaluate the number of participants discontinuing palazestrant
Trial: Progression-Free Survival (PFS)
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years)
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 or bone-only disease).
- Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy is allowed. Duration of the most recent prior ET must be at least 6 months.
- 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. Key
Exclusion criteria
- Symptomatic visceral disease, imminent organ failure, or any other reason that makes the participant ineligible for endocrine monotherapy.
- Previously received chemotherapy in the advanced/metastatic setting.
- Previously recei
Where
- Tucson, Arizona
- Fountain Valley, California
- Glendale, California
- La Jolla, California
- Los Alamitos, California
- Los Angeles, California
- Whittier, California
- Aurora, Colorado
- Denver, Colorado
- Golden, Colorado
- Grand Junction, Colorado
- Danbury, Connecticut
And 30 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 13, 2026 · Source of record for eligibility and locations