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

NCT ID: NCT01872260

Last Updated: 2026-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

255 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-22

Study Completion Date

2027-02-26

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LEE011 + letrozole Arm 1

LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

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

Letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

BYL719 + letrozole Arm 2

BYL719 - daily (dose escalating) letrozole - 2.5 mg/day

Group Type EXPERIMENTAL

Letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

BYL719

Intervention Type DRUG

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

LEE011 + BYL719 + letrozole Arm 3

LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

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

Letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

BYL719

Intervention Type DRUG

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

LEE011+ BYL719+letrozole Arm 4

LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

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

Letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

BYL719

Intervention Type DRUG

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

Interventions

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LEE011

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

Intervention Type DRUG

Letrozole

Letrozole 2.5 mg/day

Intervention Type DRUG

BYL719

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Univ of California at San Diego Moores Cancer Ctr

San Diego, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Massachusetts General Hospital SC-5

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Ctr

Nashville, Tennessee, United States

Site Status

Texas Oncology

Dallas, Texas, United States

Site Status

Mays Cancer Ctr Uthsa Mdacc

San Antonio, Texas, United States

Site Status

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status

Novartis Investigative Site

Westmead, New South Wales, Australia

Site Status

Novartis Investigative Site

Parkville, Victoria, Australia

Site Status

Novartis Investigative Site

Nedlands, Western Australia, Australia

Site Status

Novartis Investigative Site

Marseille, , France

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Saint-Herblain, , France

Site Status

Novartis Investigative Site

Pisa, PI, Italy

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Seville, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Bellinzona, , Switzerland

Site Status

Novartis Investigative Site

Glasgow, , United Kingdom

Site Status

Novartis Investigative Site

Manchester, , United Kingdom

Site Status

Countries

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United States Australia France Italy South Korea Spain Switzerland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 36800111 (View on PubMed)

Other Identifiers

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2023-509511-84-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CLEE011X2107

Identifier Type: -

Identifier Source: org_study_id

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