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

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).

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
report

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

- Has received no more than 1 prior chemotherapy 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