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

NCT ID: NCT05508906

Last Updated: 2025-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-31

Study Completion Date

2028-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a Phase 1b open-label, 2-part study in 3 treatment groups. The 3 treatment groups are as follows:

Treatment Group 1: Palazestrant (OP-1250) in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).

Treatment Group 2: Palazestrant (OP-1250) in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation).

Treatment Group 3: Palazestrant (OP-1250) in combination with everolimus.

Treatment Group 4: Palazestrant (OP-1250) in combination with atirmociclib.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Part 1 (Dose Escalation): This part will evaluate the safety and pharmacokinetics of a range of doses of palazestrant administered orally (PO) daily to subjects in combination with 600 mg of ribociclib administered PO daily for 21 consecutive days followed by 7 days off treatment (Treatment Group 1) or with 300 mg or 250 mg of alpelisib administered PO daily (Treatment Group 2) or with everolimus 10 mg administered PO daily (Treatment Group 3) and determine the RP2D (Recommended Phase 2 Dose) for each treatment group. Part 1, for Treatment Group 4, will evaluate the safety and pharmacokinetics of OP-1250 at 60 mg or 90 mg doses administered orally (PO) QD in combination with atirmociclib 300 mg PO twice a day (BID).

Part 2 (Dose Expansion): This part of the study will further evaluate the safety and PK of palazestrant at the RP2D in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3) and provide an exploratory estimate of anti-tumor activity of the combinations. An additional group of palazestrant at an alternate dose level in combination with ribociclib (Treatment Group 1b) will be explored to optimize the RP2D of palazestrant. Part 2, for Treatment Group 4, will further evaluate the safety and pharmacokinetics of atirmociclib and OP-1250 at the recommended dose for expansion.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Treatment Group 1: Palazestrant in combination with ribociclib

Treatment Group 2: Palazestrant in combination with alpelisib

Treatment Group 3: Palazestrant in combination with everolimus

Treatment Group 4: Palazestrant in combination with atirmociclib
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Palazestrant with Ribociclib

Treatment Group 1: Palazestrant in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).

Group Type EXPERIMENTAL

Palazestrant

Intervention Type DRUG

Complete estrogen receptor antagonist (CERAN)

Ribociclib

Intervention Type DRUG

All subjects in Treatment Group 1 will receive palazestrant in combination with ribociclib.

Palazestrant with Alpelisib

Treatment Group 2: Palazestrant in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation)

Group Type EXPERIMENTAL

Palazestrant

Intervention Type DRUG

Complete estrogen receptor antagonist (CERAN)

Alpelisib

Intervention Type DRUG

All subjects in Treatment Group 2 will receive palazestrant in combination with alpelisib.

Palazestrant with Everolimus

Treatment Group 3: Palazestrant in combination with everolimus

Group Type EXPERIMENTAL

Palazestrant

Intervention Type DRUG

Complete estrogen receptor antagonist (CERAN)

Everolimus

Intervention Type DRUG

All subjects in Treatment Group 3 will receive palazestrant in combination with everolimus.

Palazestrant with Atirmociclib

Treatment Group 4: Palazestrant in combination with atirmociclib

Group Type EXPERIMENTAL

Palazestrant

Intervention Type DRUG

Complete estrogen receptor antagonist (CERAN)

Atirmociclib

Intervention Type DRUG

All subjects in Treatment Group 4 will receive palazestrant in combination with atirmociclib.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Palazestrant

Complete estrogen receptor antagonist (CERAN)

Intervention Type DRUG

Ribociclib

All subjects in Treatment Group 1 will receive palazestrant in combination with ribociclib.

Intervention Type DRUG

Alpelisib

All subjects in Treatment Group 2 will receive palazestrant in combination with alpelisib.

Intervention Type DRUG

Everolimus

All subjects in Treatment Group 3 will receive palazestrant in combination with everolimus.

Intervention Type DRUG

Atirmociclib

All subjects in Treatment Group 4 will receive palazestrant in combination with atirmociclib.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

KISQALI® CDK4/6 inhibitor PIQRAY® PI3K Inhibitor mTOR inhibitor CDK4i

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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 Criteria

* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novartis

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

Olema Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Daniela Vecchio, PhD

Role: STUDY_DIRECTOR

Olema Pharmaceuticals, Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status RECRUITING

University of California San Francisco Health

San Francisco, California, United States

Site Status RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status RECRUITING

Advent Health Hematology and Oncology

Orlando, Florida, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Health

Detroit, Michigan, United States

Site Status RECRUITING

Regents of the University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University, School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Ichan School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

Henry-Joyce Cancer Clinic, The Vanderbilt Clinic

Nashville, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status RECRUITING

Macquarie Health

Sydney, New South Wales, Australia

Site Status RECRUITING

Breast Cancer Research Center- Western Australia

Nedlands, Western Australia, Australia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Australia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

OP-1250-003 Study

Role: CONTACT

415 651 7206

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Research Coordinator

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

OP-1250-003

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

PF-07104091 as a Single Agent and in Combination Therapy
NCT04553133 ACTIVE_NOT_RECRUITING PHASE2
Palbociclib With Everolimus + Exemestane In BC
NCT02871791 COMPLETED PHASE1/PHASE2