Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer
- 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.
- Short title
- Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer
- 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
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2028-01-31
- First posted
- 2022-08-19
- Registry last updated
- 2025-10-22
- Primary completion date
- 2027-12-31
- Start date
- 2022-08-31
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Olema Pharmaceuticals, Inc.
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05508906
- ClinicalTrials.gov ID
- NCT05508906
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- No masking
Dose Limiting Toxicities (DLTs)
Timeframe: The first 28 days of treatment
To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and/ or recommended dose expansion (RDE) of palazestrant when administered with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), or everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). 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, everolimus, or atirmociclib.
Timeframe: 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), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4) according to NCI-CTCAE version 5.0.
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) .
Timeframe: Every 28 days
To assess the PK of palazestrant (and potential metabolites) in combination with ribociclib (Treatment Group 1), alpelisib (Treatment Group 2), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4). Plasma levels of palazestrant will be assessed at predefined intervals to establish PK parameters (including: Cmax, Cmin, Tmax, AUC, and t1⁄2 as data permit) and palazestrant trough concentration at steady state).
Preliminarily assess the anti-tumor activity Overall Response Rate of palazestrant when administered with ribociclib, alpelisib, everolimus, or atirmociclib as assessed by the investigator using RECIST v1.1.
Timeframe: 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), or atirmociclib (Treatment Group 4).
Timeframe: 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), everolimus (Treatment Group 3), or atirmociclib (Treatment Group 4).
Timeframe: 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.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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).
- Banner MD Anderson Cancer CenterGilbert, United StatesRecruiting
- University of California San Francisco HealthSan Francisco, United StatesRecruiting
- University of Colorado Cancer CenterAurora, United StatesRecruiting
- Advent Health Hematology and OncologyOrlando, United StatesRecruiting
- University of IowaIowa City, United StatesRecruiting
- Dana Farber Cancer InstituteBoston, United StatesRecruiting
- Henry Ford HealthDetroit, United StatesRecruiting
- Regents of the University of MinnesotaMinneapolis, United StatesRecruiting
- Washington University, School of MedicineSt Louis, United StatesRecruiting
- Ichan School of Medicine at Mount SinaiNew York, United StatesRecruiting
- Atrium Health Levine Cancer InstituteCharlotte, United StatesRecruiting
- Henry-Joyce Cancer Clinic, The Vanderbilt ClinicNashville, United StatesRecruiting
- MD Anderson Cancer CenterHouston, United StatesRecruiting
- Northwest Medical SpecialtiesTacoma, United StatesRecruiting
- Macquarie HealthSydney, AustraliaRecruiting
- Breast Cancer Research Center- Western AustraliaNedlands, AustraliaRecruiting
Related records
Drugs (5)
Collaborators (2)
- Novartis
- Pfizer
Lead sponsors (1)
Conditions (2)
- Breast cancer Primary condition
- Breast neoplasm