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Phase 1b Study of Palazestrant for ER+, HER2- Breast Cancer

This study is testing a new treatment approach for advanced or metastatic (spread to other parts of the body) ER-positive, HER2-negative breast cancer. It combines palazestrant, a complete estrogen receptor antagonist (a drug that blocks estrogen's effects), with one of four other approved drugs: ribociclib, alpelisib, everolimus, or atirmociclib. Researchers want to find the safest and most effective dose of these combinations and understand any side effects. You may be eligible if you are over 18, have ER+/HER2- breast cancer, and are willing to follow study requirements. The study will look at how well the combinations are tolerated and how the drugs are processed by the body.

Study design
This is a Phase 1b, open-label study with 190 planned participants. It is divided into two parts to first find the right dose and then further evaluate safety and drug processing.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Side effects will be monitored for up to 30 days after your last dose of study drug(s). Drug levels in your body will be measured every 28 days.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05508906

Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer

Recruiting
PHASE1Ages 18+InterventionalTreatment
Olema Pharmaceuticals, Inc.
~190 participants
Updated 2025-10-22 on ClinicalTrials.gov
What's tested:PalazestrantRibociclibAlpelisibEverolimusAtirmociclib

At a glance

Recruiting sites
16 of 16 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Dose Limiting Toxicities (DLTs)
Measured over The first 28 days of treatment
+2 more outcomes measured

Conditions

Metastatic Breast Cancer
ER-positive Breast Cancer
HER2-negative Breast Cancer
Breast Cancer
Locally Advanced Breast Cancer

Explore related trials

Breast Carcinoma

Where it's being run

16 sites across 16 states
Arizona1
California1
Colorado1
Florida1
Iowa1
Massachusetts1
Michigan1
Minnesota1

Study leadership

  • Daniela Vecchio, PhD · STUDY_DIRECTOR · Olema Pharmaceuticals, Inc.

Who to contact

OP-1250-003 Study
[email protected]
415 651 7206
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Female or male aged \>18 years.
Willing and able to participate and comply with all study requirements.
Histologically- or cytologically-confirmed advanced or metastatic Breast Cancer (mBC).
ER+/HER2- disease, as determined in the most recently obtained archival tumor tissue sample from a metastatic site, using locally accepted criteria by the local pathology report.
Evaluable disease with one of the following: Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) OR patients with predominantly bone disease (with or without other non-measurable lesions) are allowed if it is possible to evaluate on radiological examinations (eg. bone scan, PET/CT, CT, MRI) even if lesions are non-measurable according to RECIST 1.1.
Life expectancy ≥6 months, as judged by the investigator.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Has received no more than 1 prior hormonal regimen (Treatment Group 1). Has received no more than 2 prior hormonal regimens (Treatment Group 2 and Treatment Group 3) . Has received no more than 2 prior hormonal regimens for metastatic disease in Part 1 (Dose Escalation) and no more than 1 prior hormonal regimes in Part 2 (Dose Expansion) for metastatic disease, regardless of type of endocrine agent (Treatment Group 4) for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed in all treatment groups. For subjects in Treatment Group 4, no prior chemotherapy for metastatic breast cancer is allowed.
Has received no more than 1 prior chemotherapy (which includes antibody drug conjugates) for locally advanced or metastatic breast cancer.

Exclusion

Prior or concurrent malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
History of cerebral vascular disease within 6 months prior to the first administration of study drug dose.
History of a pulmonary embolism, or deep venous thrombosis within the last 6 months, or subject has an increased risk of thrombosis as determined by the investigator.
History of pneumonitis or interstitial lung disease.
Leptomeningeal disease or spinal cord compression.
Medical history or ongoing gastrointestinal disorders that could affect absorption of oral therapeutics.
Known human immunodeficiency virus infection.
Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (eg, hepatitis B or hepatitis C virus), current alcohol abuse, or cirrhosis.
History of severe cutaneous reaction, such as Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms.
Active infection or at a high risk of developing a serious infection (e.g. participants with immunodeficiencies, uncontrolled diabetes mellitus, uncontrolled heart disease, poor general health, poor nutritional status).
Has clinically significant co-morbidities, such as, psychiatric disease, or any other condition that could impact the ability of the subject to participate in this study or otherwise has the potential to confound the study results.
Have received prior treatment with OP-1250.
Have received prior treatment with approved or investigational PI3K inhibitor (Treatment Group 2) or mTOR inhibitor (Treatment Group 3).

What this trial measures

  • Dose Limiting Toxicities (DLTs)The first 28 days of treatment

    To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and/ or recommended dose expansion (RDE) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). The incidence of DLTs will be assessed in the Dose Escalation part (Part 1) of the study.

  • Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of palazestrant when administered with ribociclib, alpelisib, everolimus, or atirmociclib.Up to 30 days after last dose of study drug(s) treatment

    Characterize the incidence, nature and severity of TEAEs and SAEs of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4) according to NCI-CTCAE version 5.0.

  • Pharmacokinetics (PK) of palazestrant when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4) .Every 28 days

    To assess the PK of palazestrant (and potential metabolites) in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). Plasma levels of palazestrant will be assessed at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, and t1⁄2 as data permit) and palazestrant trough concentration at steady state).