RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1b Open-Label Multicenter Study of OP-1250 (Palazestrant) in Combination With the CDK4/6 Inhibitor Ribociclib, With the PI3K Inhibitor Alpelisib, With the mTOR Inhibitor Everolimus, or With CDK4 Inhibitor Atirmociclib in Adult Subjects With Advanced and/or Metastatic ER Positive, HER2 Negative Breast Cancer

Quick Facts

Study Start:2022-08-31

Study Completion:2028-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05508906

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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).

Inclusion Criteria

Exclusion 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.

* 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).

Contacts and Locations

Study Contact

OP-1250-003 Study

CONTACT

415 651 7206

medinfo@olema.com

Principal Investigator

Daniela Vecchio, PhD

STUDY_DIRECTOR

Olema Pharmaceuticals, Inc.

Study Locations (Sites)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

United States

University of California San Francisco Health

San Francisco, California, 94158

United States

University of Colorado Cancer Center

Aurora, Colorado, 80045

United States

Advent Health Hematology and Oncology

Orlando, Florida, 32804

United States

University of Iowa

Iowa City, Iowa, 52242

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Henry Ford Health

Detroit, Michigan, 48126

United States

Regents of the University of Minnesota

Minneapolis, Minnesota, 55455

United States

Washington University, School of Medicine

St Louis, Missouri, 63110

United States

Ichan School of Medicine at Mount Sinai

New York, New York, 10029

United States

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, 28204

United States

Henry-Joyce Cancer Clinic, The Vanderbilt Clinic

Nashville, Tennessee, 37232

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Northwest Medical Specialties

Tacoma, Washington, 98405

United States

Collaborators and Investigators

Sponsor: Olema Pharmaceuticals, Inc.

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-08-31

Study Completion Date2028-01-31

Study Record Updates

Study Start Date2022-08-31

Study Completion Date2028-01-31

Terms related to this study

Additional Relevant MeSH Terms

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