A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Nonsteroidal Aromatase Inhibitor
- The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.
- The subject's breast cancer is negative for HER2.
- The subject has recurrent or metastatic breast cancer that is refractory to a
nonsteroidal aromatase inhibitor and has either disease progression or disease
- Subjects previously treated with letrozole must be able to tolerate the approved dose
and schedule of letrozole.
- For subjects enrolled in Phase 2, either archival tumor samples must be available, or
the subject must be willing to undergo a fresh biopsy.
- In Phase 2, at least 30 subjects in each arm must have measurable disease
- The subject is a postmenopausal female.
- If a subject is currently receiving bisphosphonates, the subject must have received
the bisphosphonates for at least 2 months before starting study treatment.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- The subject has adequate organ and marrow function.
- The subject has no other diagnosis of malignancy or evidence of other malignancy for
2 years before screening for this study (except non-melanoma skin cancer or in situ
carcinoma of the cervix).
- The subject is capable of understanding and complying with the protocol requirements
and has signed the informed consent document.
- The subject has received prior treatment with a selective inhibitor of PI3K, AKT,
- Certain restrictions on prior therapies apply.
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to
- The subject has untreated, symptomatic, or progressive brain metastases.
- The subject has only non-measurable lesions, other than bone, skin, or chest wall
- The subject has to start cytotoxic chemotherapy due to rapid progressive disease
involving major organs.
- The subject has prothrombin time/ International Normalized Ratio (PT/ INR) or partial
thromboplastin time (PTT) test results at screening that are above 1.3 x the
laboratory upper limit of normal.
- The subject has uncontrolled significant intercurrent illness.
- The subject has a baseline corrected QT interval (QTc) > 470 ms.
- The subject has a diagnosis of uncontrolled diabetes mellitus.
- The subject is known to be positive for the human immunodeficiency virus (HIV).
- The subject has a previously identified allergy or hypersensitivity to components of
the study treatment formulation(s).
- The subject is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee.