Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Breast Cancer

In brief

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 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.

Key facts

Study ID

NCT01872260

Run by

Novartis Pharmaceuticals

People needed

255

Starts

2013-10-22

Expected to finish

2027-02-26

Last updated by the study team

2026-06-11

Who can join

Age: 18 and older, up to 100. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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 may not qualify 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

Where it is running

• Univ of California at San Diego Moores Cancer Ctr — San Diego, California, United States
• UCSF Medical Center — San Francisco, California, United States
• H Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• Massachusetts General Hospital SC-5 — Boston, Massachusetts, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Tennessee Oncology — Nashville, Tennessee, United States
• Vanderbilt University Medical Ctr — Nashville, Tennessee, United States
• Texas Oncology — Amarillo, Texas, United States
• Mays Cancer Ctr Uthsa Mdacc — San Antonio, Texas, United States
• Northwest Medical Specialties — Tacoma, Washington, United States
• Novartis Investigative Site — Westmead, New South Wales, Australia
• Novartis Investigative Site — Parkville, Victoria, Australia
• Novartis Investigative Site — Nedlands, Western Australia, Australia
• Novartis Investigative Site — Marseille, France
• Novartis Investigative Site — Paris, France
• Novartis Investigative Site — Saint-Herblain, France
• Novartis Investigative Site — Pisa, PI, Italy
• Novartis Investigative Site — Seoul, South Korea
• Novartis Investigative Site — Madrid, Spain
• Novartis Investigative Site — Madrid, Spain
• Novartis Investigative Site — Seville, Spain
• Novartis Investigative Site — Valencia, Spain
• Novartis Investigative Site — Bellinzona, Switzerland
• Novartis Investigative Site — Glasgow, United Kingdom
• Novartis Investigative Site — Manchester, United Kingdom

Full record on ClinicalTrials.gov

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