Combination treatment for advanced breast cancer using OP-1250 with other medications

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

This study is testing a new treatment combining OP-1250 with other medications to see if it can help people with advanced breast cancer feel better and improve their condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Olema Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 16 sites (Gilbert, Arizona and 15 other locations)
• Trial ID: NCT05508906 on ClinicalTrials.gov

What this trial studies

This Phase 1b open-label study evaluates the safety and pharmacokinetics of OP-1250 in combination with ribociclib, alpelisib, or everolimus in patients with advanced or metastatic breast cancer. The study consists of two parts: the first part focuses on dose escalation to determine the recommended phase 2 dose (RP2D) for each treatment group, while the second part expands on the safety and potential anti-tumor activity of OP-1250 at the RP2D. Participants will receive daily oral doses of OP-1250 alongside the other medications for specified durations.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with histologically confirmed ER-positive, HER2-negative advanced or metastatic breast cancer.

Not a fit: Patients with non-ER-positive or HER2-positive breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced breast cancer.

How similar studies have performed: Other studies have shown promise with similar combination therapies, indicating potential for success in this approach.

Eligibility criteria

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).

Where this trial is running

Gilbert, Arizona and 15 other locations

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States (Recruiting)
• University of California San Francisco Health — San Francisco, California, United States (Recruiting)
• University of Colorado Cancer Center — Aurora, Colorado, United States (Recruiting)
• Advent Health Hematology and Oncology — Orlando, Florida, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Henry Ford Health — Detroit, Michigan, United States (Recruiting)
• Regents of the University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Washington University, School of Medicine — St Louis, Missouri, United States (Recruiting)
• Ichan School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• Atrium Health Levine Cancer Institute — Charlotte, North Carolina, United States (Recruiting)
• Henry-Joyce Cancer Clinic, The Vanderbilt Clinic — Nashville, Tennessee, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Northwest Medical Specialties — Tacoma, Washington, United States (Recruiting)
• Macquarie Health — Sydney, New South Wales, Australia (Recruiting)
• Breast Cancer Research Center- Western Australia — Nedlands, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: OP-1250-003 Study

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