Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT01872260

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–100 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Westmead, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LEE011

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

Drug

Letrozole 2.5 mg/day

BYL719

Drug

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

Primary outcomes

  1. Incidence of Dose limiting toxicities (DLTs) - Phase lb only

    Time frame: 28 days

  2. Safety and tolerability

    Time frame: 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.

  3. PK profiles of LEE011 and letrozole

    Time frame: 18 months

    To characterize PK profiles of LEE011 and Letrozole.

Secondary outcomes

  1. Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole

    Time frame: Average 24 months

    Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  2. Plasma concentration-time profiles of LEE011, BYL719 and letrozole

    Time frame: Average 24 months

    To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified.

  3. Overall Response Rate (ORR)

    Time frame: Average 24 months

    ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

  4. Duration of Response (DOR)

    Time frame: Average 24 months

    DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.

  5. Progression Free Survival (PFS)

    Time frame: Average 24 months

    PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.

  6. Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)

    Time frame: Average 24 months

    To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified.

  7. Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet

    Time frame: Average 24 months

    Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2027
Study completion
2027
First posted
Jun 7, 2013
Registry last updated
Jun 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.