Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, or Everolimus in ER+, HER2- Breast Cancer
- Conditions
- Breast CancerMetastatic Breast CancerER-positive Breast CancerHER2-negative Breast CancerLocally Advanced Breast Cancer
- Interventions
- Registration Number
- NCT05508906
- Lead Sponsor
- Olema Pharmaceuticals, Inc.
- 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.
- Detailed Description
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 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 155
- 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) for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed in all treatment groups.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Palazestrant with Ribociclib Ribociclib Treatment Group 1: Palazestrant in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation). Palazestrant with Ribociclib Palazestrant Treatment Group 1: Palazestrant in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation). Palazestrant with Everolimus Everolimus Treatment Group 3: Palazestrant in combination with everolimus Palazestrant with Alpelisib Palazestrant Treatment Group 2: Palazestrant in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation) Palazestrant with Alpelisib Alpelisib Treatment Group 2: Palazestrant in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation) Palazestrant with Everolimus Palazestrant Treatment Group 3: Palazestrant in combination with everolimus
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicities (DLTs) The first 28 days of treatment To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3). 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, or everolimus 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), or everolimus (Treatment Group 3) according to NCI-CTCAE version 5.0.
Pharmacokinetics (PK) of palazestrant when administered with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2), or everolimus (Treatment Group 3). Every 28 days To assess the PK of palazestrant (and potential metabolites) in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3). Plasma levels of palazestrant will be assessed at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, and t1⁄2) and palazestrant trough concentration at steady state).
- Secondary Outcome Measures
Name Time Method Preliminarily assess the anti-tumor activity Overall Response Rate of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3), as assessed by the investigator using RECIST v1.1. Up to 1 year Tumor response will be evaluated in patients with measurable or evaluable disease using RECISTv1.1 guidelines.
Evaluate clinical benefit rate (CBR) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3) Up to 1 year CBR will be assessed as proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) with duration of at least 24 weeks.
Evaluate duration of response (DoR) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3) Up to 1 year DoR will be calculated as the number of days from the start date of PR or CR (whichever response is achieved first) to the first date that progressive disease is documented.
Trial Locations
- Locations (16)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of California San Francisco Health
🇺🇸San Francisco, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Advent Health Hematology and Oncology
🇺🇸Orlando, Florida, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Health
🇺🇸Detroit, Michigan, United States
Regents of the University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University, School of Medicine
🇺🇸Saint Louis, Missouri, United States
Ichan School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Scroll for more (6 remaining)Banner MD Anderson Cancer Center🇺🇸Gilbert, Arizona, United StatesResearch CoordinatorContact