Recruiting
Phase 1

Ribociclib, Alpelisib, Everolimus

Sponsor:

Olema Pharmaceuticals, Inc.

Code:

NCT05508906

Conditions

Metastatic Breast Cancer

ER-positive Breast Cancer

HER2-negative Breast Cancer

Breast Cancer

Locally Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Palazestrant

Ribociclib

Alpelisib

Everolimus

Atirmociclib

Study Details

Brief summary:

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.

Conditions

Metastatic Breast Cancer

ER-positive Breast Cancer

HER2-negative Breast Cancer

Breast Cancer

Locally Advanced Breast Cancer

Study ID

NCT05508906

Start date

Aug 31, 2022

Status verified date

Oct, 2025

Completion date

Jan 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not 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).

Study Design

Enrollment

190 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Palazestrant with Ribociclib

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

experimental: Palazestrant with Alpelisib

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

experimental: Palazestrant with Everolimus

Treatment Group 3: Palazestrant in combination with everolimus

experimental: Palazestrant with Atirmociclib

Treatment Group 4: Palazestrant in combination with atirmociclib

Interventions

Palazestrant

Complete estrogen receptor antagonist (CERAN)

Ribociclib

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

Alpelisib

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

Everolimus

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

Atirmociclib

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

Primary outcome measure

  • Dose Limiting Toxicities (DLTs) [ Time Frame: The first 28 days of treatment ]
  • 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. [ Time Frame: Up to 30 days after last dose of study drug(s) treatment ]
  • 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) . [ Time Frame: Every 28 days ]

Central Contacts and Locations

Central contacts

OP-1250-003 Study

415 651 7206medinfo@olema.com

Locations

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

University of California San Francisco Health

Recruiting

San Francisco, California, United States, 94158

University of Colorado Cancer Center

Recruiting

Aurora, Colorado, United States, 80045

Advent Health Hematology and Oncology

Recruiting

Orlando, Florida, United States, 32804

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Henry Ford Health

Recruiting

Detroit, Michigan, United States, 48126

Regents of the University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Washington University, School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Ichan School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Atrium Health Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Henry-Joyce Cancer Clinic, The Vanderbilt Clinic

Recruiting

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Northwest Medical Specialties

Recruiting

Tacoma, Washington, United States, 98405

More Information

Sponsor

Olema Pharmaceuticals, Inc.

Last update posted

Oct 22, 2025

Last verified

Oct, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Olema Pharmaceuticals, Inc. on 2025-10-22.