A Phase 1b Open-Label Multicenter Study of OP-1250 in Combination with the CDK4/6 Inhibitor Ribociclib or with the PI3K Inhibitor Alpelisib in Adult Subjects with Advanced and/or Metastatic HR Positive, HER2 Negative Breast Cancer

Protocol # :
Metastatic Breast Cancer
Advanced Breast Cancer
HR-Positive Breast Cancer
HER2-negative Breast Cancer
Disease Sites
Principal Investigator
Lin, Nancy, U
Site Research Nurses
Bowers, Jordan
Campbell, Margaret
Cung, Connie
Dishman, Rachel, C.
Ficociello, Samantha
Jeon, Maryangel, H.
Kasparian, Elizabeth
Loeser, Wendy
Orechia, Meghan
Patel, Nikita
Roche, Kathleen, A.

Trial Description

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

Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals

Eligibility Requirements

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 MBC

- 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

- 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

- 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) for advanced or metastatic
disease. Prior hormonal regimens in combination with CDK4/6 inhibitors are 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

- 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