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

Phase 1/Phase 2
18 Years
Not Enrolling
Breast Cancer

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Trial Information

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

This study will investigate the combination of LEE011 (CDK4/6i) and BYL719 (PI3K-alpha-i)
with letrozole in patients with ER+/HER2- breast cancer (BC). In the Phase Ib part of the
trial, there are three dose escalation cohorts that will enroll sequentially. Part 1 is the
escalation of the double combination LEE011 + letrozole; Part 2 is the dose escalation of
the double combination of BYL719 + letrozole; The two double combinations will be followed
by the dose escalation of the triple combination of LEE011 + BYL719 with letrozole. The
three dose escalation cohorts will enroll patients with ER+/HER2- BC with any prior
endocrine therapy in the metastatic setting and up to one prior cytotoxic regimen in the
metastatic setting. Pre- and post-treatment tumor biopsies are required in the three dose
escalation cohorts. Once the RP2D/MTD of each double regimen is identified, dose expansion
cohorts of each of these two combinations will open and will enroll in the first-line
setting to confirm the doses selected in each double combination; archival tumor tissue is
required in these cohorts, although pre- and post-biopsies in these expansion cohorts are

Once the dose is identified for the triple combination, the randomized, three-arm Phase II
portion of the study will commence enrollment. This part of the trial will enroll in the
first line setting in patients with ER+/HER2- BC and will randomize patients in a 1:1:1
ratio to either double regimen (LEE011+letrozole or BYL719 +letrozole) or the triple
combination of LEE011+BYL719 with letrozole. Archival tissue is required at study entry and
biopsies in the pre- and post-treatment setting are optional in this part of the trial.

Inclusion Criteria:

- Postmenopausal, Estrogen-receptor positive breast cancer

- Phase Ib Parts 1A and 2A Expansion and Phase II only: No prior systemic treatment in
the metastatic setting.

- Phase Ib Parts 1, 2 and 3 Dose Escalation only: Any number of prior lines of
endocrine therapy is allowed with up to one prior cytotoxic regimen in the metastatic
or locally advanced setting

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 ≥ 140 mg/dL / 7.8 mmol/L), history of gestational diabetes
mellitus or documented steroid-induced diabetes mellitus.

- Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

July 2013

Completion Date:

April 2016

Related Keywords:

  • Breast Cancer
  • estrogen-receptor positive
  • Breast Neoplasms



University of Kansas Cancer Center Univ Kansas 2Kansas City, Kansas  66160
Cedars Sinai Medical Center Cedars 2Los Angeles, California  90048
Massachusetts General Hospital SC-5Boston, Massachusetts  02114
Highlands Oncology Group Oncology GroupFayetteville, Arkansas  72703
University of California at San Diego, Moores Cancer Ctr Dept. of Moores Cancer CenterSan Diego, California  92103
Indiana University Health Goshen Center for Cancer Dept of OncIndianapolis, Indiana  46202
University of Cincinnati Dept of OncologyCincinnati, Ohio  45267
Sanford Research Dept of OncologySioux Falls, South Dakota  57104
Northwest Medical Specialties Dept of OncTacoma, Washington  98405