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ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

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

A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer

NCT01872260•Novartis Pharmaceuticals

View on ClinicalTrials.gov

Summary

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.

Eligibility

Age

18 - 100 years

Sex

FEMALE

Healthy Volunteers

Inclusion Criteria

•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.

Exclusion Criteria

•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.

Locations (25)

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

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt University Medical Ctr

Nashville, Tennessee, United States

Texas Oncology

Dallas, Texas, United States

Mays Cancer Ctr Uthsa Mdacc

San Antonio, Texas, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Key Dates

Start Date

October 22, 2013

Primary Completion Date

February 26, 2027

Completion Date

February 26, 2027

Last Updated

January 30, 2026

Enrollment

255

ACTUAL participants

Conditions

Breast Cancer

Interventions

LEE011

DRUG

Letrozole

DRUG

BYL719

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 30, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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

Inclusion Criteria

Exclusion Criteria

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

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