Phase 1b Study in Combination With a CDK4/6 Inhibitor or With a PI3K Inhibitor
Study Details
Study Description
Brief Summary
This is a Phase 1b open-label, 2-part study in 2 treatment groups. The 2 treatment groups are as follows:
Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).
Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Part 1 (Dose Escalation): This part will evaluate the safety and pharmacokinetics (PK) of a range of doses of OP-1250 administered orally (PO) every day (QD) to subjects in combination with either 600 mg of ribociclib administered PO QD (Treatment Group 1) or with 300 mg of alpelisib administered PO QD (Treatment Group 2) to determine the recommended phase 2 dose (RP2D). The dose escalation phase will evaluate 3 to 6 subjects per cohort who are sequentially enrolled and monitored for DLTs during the first cycle of study treatment. Each cohort will be reviewed for safety, PK, and dose-limiting toxicity DLTs. The DLT observation may be extended to 2 cycles.
Part 2 (Dose Expansion): This part of the study will further evaluate the safety and PK of OP-1250 at the RP2D in combination with either ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2) and provide an exploratory estimate of anti-tumor activity of the combinations.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OP-1250 with Ribociclib Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation). |
Drug: OP-1250
OP-1250 is a small molecule and a CERAN being developed for the treatment of patients with advanced or metastatic HR+ and HER2- breast cancer.
Drug: Ribociclib
All subjects in Treatment Group 1 will receive OP-1250 in combination with ribociclib.
Other Names:
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| Experimental: OP-1250 with Alpelisib Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation) |
Drug: OP-1250
OP-1250 is a small molecule and a CERAN being developed for the treatment of patients with advanced or metastatic HR+ and HER2- breast cancer.
Drug: Alpelisib
All subjects in Treatment Group 2 will receive OP-1250 in combination with alpelisib.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Primary Outcome Measure [Completion of Dose Escalation to 1 cycles 28 days]
To identify the maximum tolerated dose (MTD), and/or RP2D of OP-1250 when administered in combination with ribociclibn (Treatment Group 1) or alpelisib (Treatment Group 2).
- Primary Outcome Measure [Completion of Dose Expansion up to 1 year]
To further characterize the safety and tolerability of OP-1250 at the RP2D when administered in combination with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2).
Secondary Outcome Measures
- Secondary Outcome Measure [Completion of Dose Escalation tp to 1 cycles 28 days]
To preliminarily assess the anti-tumor activity (ORR, defined as confirmed complete response [CR] + confirmed partial response [PR]) of OP-1250 when administered in combination with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2), as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).
- Secondary Outcome Measure [Completion of Dose Expansion up to 1 year]
To preliminarily assess the anti-tumor activity (ORR, defined as confirmed complete response [CR] + confirmed partial response [PR]) of OP-1250 when administered in combination with ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2), as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Female or male aged >18 years.
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Willing and able to participate and comply with all study requirements
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Histologically- or cytologically-confirmed advanced or MBC
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HR+/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
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Evaluable disease (measurable and non-measurable): 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).-Subject must have received at least 6 months of a prior continuous endocrine therapy for locally advanced or metastatic breast cancer
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Life expectancy ≥6 months, as judged by the investigator
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
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Has received no more than 2 prior hormonal regimens for advanced or metastatic disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are allowed.
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Has received no more than 1 prior chemotherapy for locally advanced or metastatic breast cancer.
Exclusion Criteria:
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Prior or concurrent malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen
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Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
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History of cerebral vascular disease within 6 months prior to the first administration of study drug dose
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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
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History of pneumonitis or interstitial lung disease
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Leptomeningeal disease or spinal cord compression
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Medical history or ongoing gastrointestinal disorders that could affect absorption of oral therapeutics
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Known human immunodeficiency virus infection
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Olema Pharmaceuticals, Inc.
- Novartis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OP-1250-003