NCT01872260

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

Active, enrolled Phase 1, PHASE2 Last updated 1 April 2026

What this trial tests

Phase 1, PHASE2 trial testing LEE011 in Breast Cancer in 255 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

22 October 2013

Primary endpoint
26 February 2027

26 February 2027

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 1, PHASE2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	255
Start date	22 October 2013
Primary completion	26 February 2027
Estimated completion	26 February 2027
Sites	25 locations across South Korea, Spain, United Kingdom, Australia, United States, Italy, France, Switzerland

Drugs / interventions tested

• LEE011 (LEE011) — full drug profile →
• Letrozole — full drug profile →
• BYL719 — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 100, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cell cycle proteins as promising targets in cancer therapy.
   Otto T, Sicinski P. · · 2017 · cited 1412× · PMID 28127048 · DOI 10.1038/nrc.2016.138
2. The history and future of targeting cyclin-dependent kinases in cancer therapy.
   Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. · · 2015 · cited 1349× · PMID 25633797 · DOI 10.1038/nrd4504
3. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
   Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
4. Targeting CDK4 and CDK6: From Discovery to Therapy.
   Sherr CJ, Beach D, Shapiro GI. · · 2016 · cited 729× · PMID 26658964 · DOI 10.1158/2159-8290.cd-15-0894
5. Cyclin D1, cancer progression, and opportunities in cancer treatment.
   Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
6. CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought.
   Klein ME, Kovatcheva M, Davis LE, Tap WD, et al · · 2018 · cited 308× · PMID 29731395 · DOI 10.1016/j.ccell.2018.03.023
7. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers.
   Finn RS, Aleshin A, Slamon DJ. · · 2016 · cited 254× · PMID 26857361 · DOI 10.1186/s13058-015-0661-5
8. A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer.
   Mayer IA, Abramson VG, Formisano L, Balko JM, et al · · 2017 · cited 245× · PMID 27126994 · DOI 10.1158/1078-0432.ccr-16-0134