LEE011 + BYL719 + Letrozole for Breast Cancer

Recruiting at38 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Novartis Pharmaceuticals

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for postmenopausal women with advanced ER+/HER2- breast cancer who haven't had systemic treatment in the advanced setting, except possibly letrozole for up to one month. They can have had (neo)adjuvant therapy if they've been disease-free for over a year since completion. Exclusions include recent major surgery, other cancers within 3 years, heart issues, active brain metastases, and certain diabetes conditions.

Inclusion Criteria

I had early-stage breast cancer treatment and have been disease-free for over a year.

I may have had multiple hormone treatments but only one chemotherapy for advanced cancer.

I haven't had systemic treatment for advanced cancer, except possibly letrozole for up to a month.

Exclusion Criteria

My heart does not function properly.

I have diabetes or had gestational diabetes.

I have pancreatitis.

Treatment Details

Interventions

• BYL719 (PI3K-alpha Inhibitor)
• LEE011 (CDK4/6 Inhibitor)
• Letrozole (Aromatase Inhibitor)

Trial Overview The study tests two drugs: LEE011 (a CDK4/6 inhibitor) and BYL719 (a PI3K-alpha inhibitor), both combined with letrozole. It's an open-label Phase Ib trial aiming to find the maximum tolerated doses of these combinations and their preliminary effectiveness against breast cancer.

Participant Groups

Group I: LEE011+ BYL719+letrozole Arm 4 Experimental Treatment 3 Interventions

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

Group II: LEE011 + letrozole Arm 1 Experimental Treatment 2 Interventions

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

Group III: LEE011 + BYL719 + letrozole Arm 3 Experimental Treatment 3 Interventions

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

Group IV: BYL719 + letrozole Arm 2 Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD