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

NCT01872260 · tracked via the Priya Life Science UK tracker

Sponsor

Novartis Pharmaceuticals

Phase

Phase 1/2

Started

2013-10-22

Last updated

2026-09-18

Condition(s) studied

Breast Cancer

Investigational drug(s) / intervention(s)

LEE011LetrozoleBYL719

LEE011: LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4.

Letrozole: Letrozole 2.5 mg/day

BYL719: BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4

Study 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

Sex

FEMALE

Min age

18 Years

Max age

100 Years

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. * Other protocol-defined inclusion/exclusion criteria may apply

Primary outcome measure(s)

Incidence of Dose limiting toxicities (DLTs) - Phase lb only — 28 days
Safety and tolerability — Average 18 months
Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
PK profiles of LEE011 and letrozole — 18 months
To characterize PK profiles of LEE011 and Letrozole.

Trial sites (25)

Facility	City	Region
Univ of California at San Diego Moores Cancer Ctr	San Diego	California
UCSF Medical Center	San Francisco	California
H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
Massachusetts General Hospital SC-5	Boston	Massachusetts
Massachusetts General Hospital	Boston	Massachusetts
Tennessee Oncology	Nashville	Tennessee
Vanderbilt University Medical Ctr	Nashville	Tennessee
Texas Oncology	Amarillo	Texas
Mays Cancer Ctr Uthsa Mdacc	San Antonio	Texas
Northwest Medical Specialties	Tacoma	Washington
Novartis Investigative Site	Westmead	New South Wales
Novartis Investigative Site	Parkville	Victoria
Novartis Investigative Site	Nedlands	Western Australia
Novartis Investigative Site	Marseille	France
Novartis Investigative Site	Paris	France
Novartis Investigative Site	Saint-Herblain	France
Novartis Investigative Site	Pisa	PI
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

More Novartis Pharmaceuticals trials in the UK

Asciminib Roll-over Study Recruiting

Open-label, Long-term Safety Study of Secukinumab in Polymyalgia Rheumatica (PMR) Active, not recruiting

A Randomized, Double-blind 2-arm, Followed by an Open-label 1-arm, NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome. Active, not recruiting

Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2) Active, not recruiting

Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome Active, not recruiting

Other trials for the same condition

A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer Active, not recruiting

Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1) Active, not recruiting

Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756) Active, not recruiting

Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Active, not recruiting

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT01872260 on ClinicalTrials.gov ↗ ← All trials in the UK