A Phase 3 interventional study of Palazestrant and Letrozole-matching placebo in Breast Cancer, Locally Advanced Breast Cancer and Metastatic Breast Cancer, sponsored by Olema Pharmaceuticals, Inc.. Recruiting at 200 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by Olema Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment
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.
This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm).
This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's planned enrollment of 1,000 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Olema Pharmaceuticals, Inc. is the lead sponsor of 6 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive palazestrant, ribociclib and letrozole-matching placebo
Drug: Palazestrant · Drug: Letrozole-matching placebo · Drug: Ribociclib
Participants will receive letrozole, ribociclib and palazestrant-matching placebo
Drug: Ribociclib · Drug: Letrozole · Drug: Palazestrant matching-placebo
Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
Also known as: OP-1250
Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle
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.
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)
Overall Survival (OS)
To compare OS between investigational and control arms.
Time frame: From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)
Progression Free Survival (PFS)
To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)
Overall response Rate (ORR)
To evaluate ORR based on Blinded Independent Review Committee (BIRC) assessment
Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)
Duration of Response (DOR)
To evaluate DOR based on Blinded Independent Review Committee (BIRC) assessment
Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)
Clinical Benefit Rate (CBR)
To evaluate CBR based on Blinded Independent Review Committee (BIRC) assessment
Time frame: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)
Overall response Rate (ORR)
To evaluate ORR based on local investigator assessment
Time frame: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)
Duration of Response (DOR)
To evaluate DOR based on local investigator assessment
Time frame: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)
Clinical Benefit Rate (CBR)
To evaluate CBR based on local investigator assessment
Time frame: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)
Safety and tolerability
To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements
Time frame: Up to 42 days after end of treatment (estimated as up to 3.5 years)
Pharmacokinetics (PK) of palazestrant and ribociclib
To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters
Time frame: Every 28 days (estimated as up to 3.5 years)
Health-related patient-reported outcomes (PROs)
To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials
Time frame: Every 28 days (estimated as up to 3.5 years)
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Plan to share: No
Started Nov 2025 (actual). Primary completion is estimated for Dec 2028, 37 months after the start.
Of 272 industry-sponsored phase 3 interventional studies under Breast Neoplasms, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 63. This study's planned 37 months is close to that.
Counting every sponsor, half of 600 studies reached it within 59 months; a quarter within 36 and three quarters within 96.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drug tested here: Palazestrant
Olema Pharmaceuticals, Inc.