Breast CancerPhase 1/2NCT01872260
Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
A Phase 1/2 study testing LEE011, Letrozole and BYL719 in people with Breast Cancer, run by Novartis Pharmaceuticals at 25 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- LEE011, Letrozole and BYL719
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- 25 sitesin 8 countries
- Study dates
- 22 Oct 2013to 26 Feb 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
25 sites in 8 countries.
25 sites in 8 countries
United States10 sites
Texas Oncology
Amarillo, Texas, 79124
Massachusetts General Hospital SC-5
Boston, Massachusetts, 02114
Massachusetts General Hospital
Boston, Massachusetts, 02114
Tennessee Oncology
Nashville, Tennessee, 37203
Vanderbilt University Medical Ctr
Nashville, Tennessee, 37232
Mays Cancer Ctr Uthsa Mdacc
San Antonio, Texas, 78229
Univ of California at San Diego Moores Cancer Ctr
San Diego, California, 92103
UCSF Medical Center
San Francisco, California, 94143
Northwest Medical Specialties
Tacoma, Washington, 98405
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Spain4 sites
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Seville, 41013
Novartis Investigative Site
Valencia, 46010
Australia3 sites
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
Parkville, Victoria, 3050
Novartis Investigative Site
Westmead, New South Wales, 2145
France3 sites
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Saint-Herblain, 44805
United Kingdom2 sites
Novartis Investigative Site
Glasgow, G12 0YN
Novartis Investigative Site
Manchester, M20 2BX
About this study
Official title: 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).
Read more
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.
- Conditions
- Breast Cancer
- Being tested
- LEE011, Letrozole, BYL719
- Keywords
- Hormone-receptor positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011Drug
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4.
LetrozoleDrug
Letrozole 2.5 mg/day
BYL719Drug
BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4
| Study group | Role | What they receive |
|---|---|---|
| LEE011 + letrozole Arm 1 | Experimental | LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day Receives: Drug: LEE011; Drug: Letrozole |
| BYL719 + letrozole Arm 2 | Experimental | BYL719 - daily (dose escalating) letrozole - 2.5 mg/day Receives: Drug: Letrozole; Drug: BYL719 |
| LEE011 + BYL719 + letrozole Arm 3 | Experimental | LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day Receives: Drug: LEE011; Drug: Letrozole; Drug: BYL719 |
| LEE011+ BYL719+letrozole Arm 4 | Experimental | LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day Receives: Drug: LEE011; Drug: Letrozole; Drug: BYL719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Measured: 28 days
Safety and tolerability
Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
Measured: Average 18 months
PK profiles of LEE011 and letrozole
To characterize PK profiles of LEE011 and Letrozole.
Measured: 18 months
Secondary outcomes (7)
Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole
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
Measured: Average 24 months
Plasma concentration-time profiles of LEE011, BYL719 and letrozole
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.
Measured: Average 24 months
Overall Response Rate (ORR)
ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
Measured: Average 24 months
Duration of Response (DOR)
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.
Measured: Average 24 months
Progression Free Survival (PFS)
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.
Measured: Average 24 months
Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)
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.
Measured: Average 24 months
Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet
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
Measured: Average 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2013 (estimated)
- Study start22 Oct 2013
- Primary completion26 Feb 2027 (estimated)
- Study completion26 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01872260
- Sponsor's protocol ID
- CLEE011X2107
- Other IDs
- 2023-509511-84-00, 2023
- Status last verified
- Sep 2026
- First submitted
- 30 May 2013
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
- Expanded access
- Available
Publications
Ji Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23.
PubMed 42334791Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.
PubMed 36800111
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer
- ClinicalTrials.gov ID
- NCT01872260
- Acronym / sponsor ID
- CLEE011X2107
- Conditions
- Breast Cancer
- Keywords
- Hormone-receptor positive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 Oct 2013 (actual)
- Primary completion
- 26 Feb 2027 (estimated)
- Study completion
- 26 Feb 2027 (estimated)
- First posted
- 7 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LEE011 + letrozole Arm 1 | Experimental | Drug: LEE011, Drug: LetrozoleLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day |
| BYL719 + letrozole Arm 2 | Experimental | Drug: Letrozole, Drug: BYL719BYL719 - daily (dose escalating) letrozole - 2.5 mg/day |
| LEE011 + BYL719 + letrozole Arm 3 | Experimental | Drug: LEE011, Drug: Letrozole, Drug: BYL719LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day |
| LEE011+ BYL719+letrozole Arm 4 | Experimental | Drug: LEE011, Drug: Letrozole, Drug: BYL719LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEE011LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4. | Drug | LEE011 + BYL719 + letrozole Arm 3, LEE011 + letrozole Arm 1, LEE011+ BYL719+letrozole Arm 4 |
| LetrozoleLetrozole 2.5 mg/day | Drug | BYL719 + letrozole Arm 2, LEE011 + BYL719 + letrozole Arm 3, LEE011 + letrozole Arm 1, LEE011+ BYL719+letrozole Arm 4 |
| BYL719BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4 | Drug | BYL719 + letrozole Arm 2, LEE011 + BYL719 + letrozole Arm 3, LEE011+ BYL719+letrozole Arm 4 |
Primary outcome
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Time frame: 28 days
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.
PK profiles of LEE011 and letrozole
Time frame: 18 months
To characterize PK profiles of LEE011 and Letrozole.
7 secondary outcomes
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
Plasma concentration-time profiles of LEE011, BYL719 and letrozole
Time frame: Average 24 months
Overall Response Rate (ORR)
Time frame: Average 24 months
Duration of Response (DOR)
Time frame: Average 24 months
Progression Free Survival (PFS)
Time frame: Average 24 months
Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)
Time frame: Average 24 months
Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet
Time frame: Average 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Derived from this study: PubMed 42334791Ji Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23.
- Derived from this study: PubMed 36800111Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
25 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LEE011, Letrozole and BYL719 in people with Breast Cancer, run by Novartis Pharmaceuticals at 25 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Spain, Australia, France, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose limiting toxicities (DLTs) - Phase lb only (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01872260, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.