The purpose of this trial is to inform the future clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor). This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole (Arms 3 and 4). The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover for patients who have progressed while on dose escalation or dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted after protocol amendment 6. Approximately 225 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.
A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer
Breast CancerHormone-receptor positiveLetrozole
You can join if…
Open to females ages 18 years and up
Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive breast cancer
Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.
Phase Ib dose expansions Arms 1, 2 and 3
No prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole for a maximum of one month prior to starting study treatment.
Patients who received (neo)adjuvant therapy for breast cancer are eligible. Prior therapy with letrozole or anastrozole in the (neo)adjuvant setting is permitted if the disease-free interval is greater than 12 months from the completion of treatment.
You CAN'T join if...
HER2-overexpression in the patient's tumor tissue
Patients with active CNS or other brain metastases
Major surgery within 2 weeks
Acute or chronic pancreatitis
Bilateral diffuse lymphangitic carcinomatosis
Another malignancy within 3 years
Receiving hormone replacement therapy that cannot be discontinued
Impaired cardiac function
Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose ≥ 126 mg/dL / 7.0 mmol/L or hemoglobin A1c>6.5%), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
Other protocol-defined inclusion/exclusion criteria may apply
University of California San Francisco Onc Deptaccepting new patients San Francisco, California, 94101, USA
University of California at San Diego, Moores Cancer Ctr Dept. of Moores Cancer Centeraccepting new patients San Diego, California, 92103, USA