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
2 other identifiers
interventional
255
8 countries
25
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 breast-cancer
Started Oct 2013
Longer than P75 for phase_1 breast-cancer
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 30, 2013
CompletedFirst Posted
Study publicly available on registry
June 7, 2013
CompletedStudy Start
First participant enrolled
October 22, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 26, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 26, 2027
April 1, 2026
March 1, 2026
13.4 years
May 30, 2013
March 31, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
28 days
Safety and tolerability
Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
Average 18 months
PK profiles of LEE011 and letrozole
To characterize PK profiles of LEE011 and Letrozole.
18 months
Secondary Outcomes (7)
Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole
Average 24 months
Plasma concentration-time profiles of LEE011, BYL719 and letrozole
Average 24 months
Overall Response Rate (ORR)
Average 24 months
Duration of Response (DOR)
Average 24 months
Progression Free Survival (PFS)
Average 24 months
- +2 more secondary outcomes
Study Arms (4)
LEE011 + letrozole Arm 1
EXPERIMENTALLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day
BYL719 + letrozole Arm 2
EXPERIMENTALBYL719 - daily (dose escalating) letrozole - 2.5 mg/day
LEE011 + BYL719 + letrozole Arm 3
EXPERIMENTALLEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day
LEE011+ BYL719+letrozole Arm 4
EXPERIMENTALLEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day
Interventions
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4.
Letrozole 2.5 mg/day
BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4
Eligibility Criteria
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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
Univ of California at San Diego Moores Cancer Ctr
San Diego, California, 92103, United States
UCSF Medical Center
San Francisco, California, 94143, United States
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Massachusetts General Hospital SC-5
Boston, Massachusetts, 02114, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Ctr
Nashville, Tennessee, 37232, United States
Texas Oncology
Amarillo, Texas, 79124, United States
Mays Cancer Ctr Uthsa Mdacc
San Antonio, Texas, 78229, United States
Northwest Medical Specialties
Tacoma, Washington, 98405, United States
Novartis Investigative Site
Westmead, New South Wales, 2145, Australia
Novartis Investigative Site
Parkville, Victoria, 3050, Australia
Novartis Investigative Site
Nedlands, Western Australia, 6009, Australia
Novartis Investigative Site
Marseille, 13273, France
Novartis Investigative Site
Paris, 75475, France
Novartis Investigative Site
Saint-Herblain, 44805, France
Novartis Investigative Site
Pisa, PI, 56126, Italy
Novartis Investigative Site
Seoul, 03080, South Korea
Novartis Investigative Site
Madrid, 28009, Spain
Novartis Investigative Site
Madrid, 28050, Spain
Novartis Investigative Site
Seville, 41013, Spain
Novartis Investigative Site
Valencia, 46010, Spain
Novartis Investigative Site
Bellinzona, 6500, Switzerland
Novartis Investigative Site
Glasgow, G12 0YN, United Kingdom
Novartis Investigative Site
Manchester, M20 2BX, United Kingdom
Related Publications (1)
Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.
PMID: 36800111DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 30, 2013
First Posted
June 7, 2013
Study Start
October 22, 2013
Primary Completion (Estimated)
February 26, 2027
Study Completion (Estimated)
February 26, 2027
Last Updated
April 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com