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

Status:	Active, not recruiting
Conditions:	Breast Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	2/22/2019
Start Date:	October 22, 2013
End Date:	December 31, 2019

A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With 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.

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

We found this trial at

sites

Vanderbilt University Medical Center Vanderbilt - Thompson Ln

Nashville, Tennessee 37232

Principal Investigator: Ingrid A. Mayer

Phone: 615-936-1164

from

Nashville, TN