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LEE011

Phase 3

Breast Cancer | Small molecule | Oncology |Novartis AG|Last Updated: Jul 8, 2026

Target and mechanism

Molecular targetCDK6, CDK4
Target classInhibitor
ModalitySmall molecule

Also known as Ribociclib, ribociclib, Ribociclib (neoadjuvant)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials12
Total Enrollment4,870

FDA Designations

RARE_PEDIATRIC_DISEASE

Clinical trial landscape

LEE011 · 22 trials · 16 indications

Phase 3 2Phase 2 7Phase 1 13
NCT03462251Ribociclib and Endocrine Therapy or Chemotherapy With or Without Bevacizumab for Metastatic Breast Cancer in First LineBreast Cancer
COMPLETED41 Analytics
NCT02941926Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBCBreast Cancer
COMPLETED3,246 Analytics
PHASE3COMPLETED
Ribociclib and Endocrine Therapy or Chemotherapy With or Without Bevacizumab for Metastatic Breast Cancer in First Line
Breast CancerUnlock trial analytics
PHASE3COMPLETED
Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC
Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Efficacy in terms of PFS
Up to approximately 15 months.

PFS is defined as time from randomization to progression of disease or death of any cause, whichever comes first. It will be assessed by imaging until progressive disease or start of next-line therapy.

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase
From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.

AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.

Overall Response Rate (ORR)
Up to 23.8 months

ORR defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by local investigators according to RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Progression-free Survival
Up to approximately 34 months

Progression-free survival was defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed at the time of last patient, last visit (LPLV).

Pre and Postmenopausal Cohorts: Progressive Free Survival (PFS) Based on Local Assessment by RECIST 1.1 Guideline
After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.

Progression-free survival (PFS) was defined as the time from randomization to the first documented disease progression or death from any cause. PFS was assessed by local investigators based on tumor evaluations using RECIST version 1.1 criteria. Patients who had not experienced progression or death by the analysis cut-off date of 25 April 2022 were censored at the date of their last adequate tumor assessment prior to that cut-off.

Number of Participants With Adverse Events and Serious Adverse Events
Up to 26 months

These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

Percentage of Participants With Adverse Events and Serious Adverse Events
Up to 26 months

These are the percentage of participants that had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

Number of Patients enrolled and received LEE011
up to 5 years (study duration)

Continued access to study treatment as a single agent or in combination with other investigational treatments until patients discontinue study

Length of time receiving study treatment
up to 5 years (study duration)

Assessed by duration in days from start of study treatment until study treatment discontinuation

Progression Free Survival (PFS)
At 24 months

Date of randomization to the date of the first documented progression or death due to any causeas per RECIST v1.1 (by local investigator assessment). Only includes data prior to cross over. Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.

Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
Baseline up ≥16 weeks up to approximately 36 months

Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS

Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS
Baseline and ≥ 16 weeks up to approximately 36 months

CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS

Overall Response Rate (ORR) ≥ 16 Weeks. FAS
Baseline and ≥ 16 weeks up to approximately 36 months

ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS

Cohort A: Recommended Phase2 Dose (RP2D)
Disease was evaluated at baseline and each cycle on treatment and the end of treatment. Toxicity was evaluated each cycle on treatment, end of treatment and 30 days follow-up. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Standard 3+3 phase-I design will be utilized in this trial. Briefly, a minimum of 3 evaluable patients will be entered at first dose level (=300 mg ribociclib) and T-DM1 (3.6 mg/kg IV). If 1 out of the first 3 patients enrolled experiences a dose-limiting toxicity (DLT), 3 additional patients will be enrolled to that dose level. If no more than 1 patient in 6 experiences a DLT, dose escalation of ribociclib will continue to next dose-level. If 2 or more patients at any given dose level experience a DLT, dose escalation will stop and the Recommended Phase2 Dose (RP2D) will be defined. Maximum dose-escalation of Ribociclib (LEE011) will be up to 600 mg.

Cohort B: Clinical Benefit Rate (CBR)
at week 12

CBR is defined as the proportion of patients with a complete response (CR) or partial response (PR), or with stable disease (SD) at week 24 by RECIST 1.1 criteria. CBR will be reported with 90% confidence interval, adjusting for two-stage design using the method from Atkinson and Brown.

Cohort C: Clinical Benefit Rate (CBR)
at week 12

CBR is defined as the proportion of patients with a complete response (CR) or partial response (PR), or with stable disease (SD) at week 24 by RECIST 1.1 criteria. CBR will be reported with 90% confidence interval, adjusting for two-stage design using the method from Atkinson and Brown.

Phase I: Determine the Recommended Phase II Dose (RP2D)
First 4 weeks of treatment

Determine the Recommended Phase II dose (RP2D) of LEE011 (ribociclib) in the combination with everolimus in patients with mPAC refractory to 5-FU- and GEM-based chemotherapy based on DLTs within the first 4 weeks of treatment.

Phase II: Progression-free Survival (PFS) Rate at 8 Weeks
8 weeks

PFS at 8 weeks in a patient with refractory mPAC treated with LEE011 and everolimus, defined as positive if a patient does not have evidence of progressive disease at 8 weeks as measured by expert radiologists using RECIST v1.1 criteria

Determination of the maximum tolerated dose (MTD) and the recommended dose for phase 2 (RP2D) of ribociclib and capecitabine combination
From baseline to the end of cycle 1, up to 21 days

Determination of MTD and RP2D of ribociclib and capecitabine combination, PO in a 21 day schedule (2 weeks on/1 week off), in subjects eligible to a capecitabine treatment, with locally advanced/metastatic breast cancer who failed anthracycline and taxane treatment.

Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I
Baseline up to 28 days

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a reasonably possible relationship to the study medication(s) and is unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment (cycle 1) and meets any of the criteria defined in the protocol. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

Clinical Benefit Rate as Per Central Review by Group- Phase II
From baseline up to 24 weeks

Clinical Benefit Rate (CBR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) or with stable disease (SD) as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response or Non-Progressive Disease (NCRNPD) during first 24 weeks of first dose. CR=disappearance of all non-nodal target lesions, PR=at least a 30% decrease in the sum of diameter of all target lesions, SD=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD), PD=at least a 20% increase in the sum of diameter of all target lesions. The hypothesis was to be rejected if the lower limit of the 95% Confidence Interval for Clinical Benefit Rate (CBR) was greater than 10%.

Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II
Baseline up to 24 weeks and at 24 weeks

Complete response (CR) or partial response (PR), or stable disease (SD) at 24 weeks as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Non-CR Non-PD (NCRNPD) at Week 24.

Primary Pharmacokinetics (PK) parameters of LEE011 when appropriate
14 days

Primary composite PK parameters: Cmax, AUClast, AUCinf, and CL/F. To determine the impact of various degrees of renal impairment on primary PK parameters of LEE011 following a single 400mg oral dose

Composite Pharmacokinetic (PK) profile of a single oral dose of LEE011 in subjects with impaired hepatic function as compared to healthy subjects with normal hepatic function.
14 days

PK profile includes the following parameters Tmax, Cmax, AUClast, AUCinf, T1/2, CL/F, Vz/F.

Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs)
first cycle (28 days)

DLTs at each dose level associated with administration of LEE011 and letrozole

Phase Ib Dose Expansion: Number of participants with adverse events (AEs)
18 months

This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant

Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)
18 months

This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant

Incidence of dose-limiting toxicities (DLTs)
28 days

Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle

Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
approximately 25 months

Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability.

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

Dose limiting toxicities

Progression free survival (PFS) - Phase ll only
36 months

Progression Free Survival per RECIST v 1.1 by local investigator assessment

Safety and tolerability
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
18 months

To characterize PK profiles of LEE011 and Letrozole.

Dose Escalation: Incidence of Dose Limiting Toxicity (DLT)
At the end of Cycle 1 (each cycle is 28 days)

DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria.

Dose Expansion: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Approximately 4.5 years after FPFV

Adverse events were collected for approximately 4.5 years for dose expansion including the 30 days safety follow-up period.

Incidence of dose limiting toxicities (DLTs)
First cycle (28 days)
Maximum tolerated dose (MTD) and/or recomended dose (RD)
First cycle (28 days)
Primary Outcome Measures: Maximum tolerated dose of LEE011 when administered orally once daily, as assessed by Frequency of DLTs as a function of LEE011 dose
12 month

Secondary Endpoints

Overall Survival (OS)
Up to approximately 48 months.
Overall Response Rate (ORR)
Up to approximately 15 months.
Clinical Benefit Rate (CBR)
Up to approximately 15 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm AEXPERIMENTALCombination of ribociclib and aromatase inhibitor or fulvestrant
Arm BACTIVE_COMPARATORCapecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Ribociclib + letrozole+goserelin/leuprolideEXPERIMENTALParticipants received ribociclib (orally taken, 3 weeks on/1 week off) in combination with letrozole (orally taken once daily). For men and premenopausal women, either goserelin was given as an injectable subcutaneous implant or leuprolide was given as an intramuscular injection.
Ribociclib 400 mgEXPERIMENTALRibociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
Ribociclib 600 mgACTIVE_COMPARATORRibociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
Combination ChemotherapyACTIVE_COMPARATORCombination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine were administered to patients enrolled in the control group. The chemotherapy regimen was decided by the treating physician.
RibociclibEXPERIMENTALPatients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm. Premenopausal experimental arm: Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Ribociclib. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and \< 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history. Postmenopausal experimental arm: Letrozole + Ribociclib. Pharmacokinetic (PK) Cohort: Open-label treatment with Ribociclib + Letrozole combination. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.
Ribociclib PlaceboPLACEBO_COMPARATORPatients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm. Premenopausal control arm: Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Placebo. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and \< 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history. Postmenopausal control arm: Letrozole + Placebo. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.
Ribociclib + adjuvant endocrine therapy (ET)EXPERIMENTALPatients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)
Placebo + adjuvant endocrine therapy (ET)PLACEBO_COMPARATORPatients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
LEE011EXPERIMENTALAll patients in all combinations with LEE011 will be entered in one arm.
Placebo ArmPLACEBO_COMPARATOR600 mg daily dosing days 1-21 of a 28 day cycle
Cohort A: Ribociclib + T-DM1 [3+3 Design]EXPERIMENTAL* Ribociclib will be given orally once day (day 5-18) at a pre-determine dose for two weeks of a 21 day cycle. During dose escalation, patients received doses of ribociclib of Period 1: 300 mg (n = 3), Period 2: 400 mg (n = 3), Period 3: 500 mg (n = 3), and Period 4: 600 mg (n = 3). Maximum dose-escalation of Ribociclib will be up to 600 mg. Dose-escalation will stop if DLT exceed limit. * T-DM1 will be given as IV infusions on Day 1 of a 3 week cycle at a pre-determined dose over pre-determined period of time.
Cohort B: Ribociclib + Trastuzumab [Phase 1b/2 Study]EXPERIMENTAL* Ribociclib will be given orally once day (400 mg per day on a continuous schedule) for a 21-day cycle of treatment. * Trastuzumab will be given as IV infusions over 6 mg/kg every 3 weeks.
Cohort C: Ribociclib + Trastuzumab + Fulvestrant [Phase 1b/2 Study]EXPERIMENTAL* Ribociclib will be given orally once a day continuously for a 28-day cycle of treatment (except at Dose Level -1, when Ribociclib is given Days 1-21 of a 28 day cycle). * Trastuzumab will be given as IV infusions over a pre-determined period of time and dose. Fulvestrant will be dosed approximately every 28 days as per standard of care.
Phase I - Dose Level 1EXPERIMENTALTreatment cycles are 28 days long. LEE011 (taken orally) - 250mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28
Phase I - Dose Level 2EXPERIMENTALTreatment cycles are 28 days long. LEE011 (taken orally) - 300mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28
Phase I - Dose Level -1EXPERIMENTALTreatment cycles are 28 days long. LEE011 (taken orally) - 200mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28
Phase I - Dose Level -2EXPERIMENTALTreatment cycles are 28 days long. LEE011 (taken orally) - 150mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28
Phase II - DoseEXPERIMENTALTreatment cycles are 28 days long. LEE011 (taken orally) - the recommended phase II dose Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28
combination of ribociclib + capecitabineEXPERIMENTALRIBOCICLIB from 200 to 600mg once daily + CAPECITABINE from 750 to 1000 mg/m² BID, cycles are defined in 21-day periods, 2 weeks on treatment, 1 week off treatment
Cohort AEXPERIMENTALRibociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B
Cohort BEXPERIMENTALRibociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally
Cohort CEXPERIMENTALRibociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Group 1EXPERIMENTALRibociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally
Group 2EXPERIMENTALRibociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Normal renal functionEXPERIMENTALNormal renal function; matched demography to renal impariment cohorts
Severe renal impairmentEXPERIMENTALSevere decrease in GFR (15-29 ml/min)
End Stage Renal DiseaseEXPERIMENTALEnd stage renal disease not on dialysis; GFR \<15 ml/min
Mild renal impairmentEXPERIMENTALMild decrease in GFR (60-89 ml/min)
Moderate renal impairmentEXPERIMENTALModerate decrease in GFR (30-59 ml/min)
Normal Hepatic FunctionEXPERIMENTALNormal hepatic function; matched demography to hepatic impairment cohorts
Mild Hepatic ImpairmentEXPERIMENTALChild-Pugh Classification A (score 5-6)
Moderate Hepatic ImpairmentEXPERIMENTALChild-Pugh Classification B (score 7-9)
Severe Hepatic ImpairmentEXPERIMENTALChild-Pugh Classification C (score 10-15)
LEE011 +LetrozoleEXPERIMENTALLEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily
LEE011 + TamoxifenEXPERIMENTALLEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily
LEE011 + FulvestrantEXPERIMENTALLEE011 - 3 weeks on 1 week off Fulvestrant 500 mg - Dosed every 28 days (Day 1 for each cycle) with 1 additional dose on Day 15 of Cycle 1
LEE011 + buparlisib + letrozoleEXPERIMENTALopen label, dose escalation evaluating max tolerated dose of the triple combination
LEE011 + BKM120 + fulvestrantEXPERIMENTALLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
LEE011 + BYL719 + fulvestrantEXPERIMENTALLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
LEE011 + letrozole Arm 1EXPERIMENTALLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day
BYL719 + letrozole Arm 2EXPERIMENTALBYL719 - daily (dose escalating) letrozole - 2.5 mg/day
LEE011 + BYL719 + letrozole Arm 3EXPERIMENTALLEE011 - 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 4EXPERIMENTALLEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day
L-R-E armEXPERIMENTALParticipants who took ribociclib (LEE011), everolimus (RAD001) and exemestane triple combination
L-E armEXPERIMENTALParticipants who ribociclib (LEE011) and exemestane double combination

Interventions

NameTypeDescription
Ribociclib and aromatase inhibitor or fulvestrantCOMBINATION_PRODUCTCombination of ribociclib and aromatase inhibitor or fulvestrant
Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumabCOMBINATION_PRODUCTCapecitabine with bevacizumab OR Paclitaxel with or without bevacizumab
RibociclibDRUGRibociclib was centrally supplied to the investigators and administered orally once a day on days 1-21 of each 28 day cycle at a starting dose of 600 mg daily
LetrozoleDRUGLetrozole was procured locally and administered orally once a day on a continuous daily schedule at a dose of 2.5 mg
GoserelinDRUGGoserelin was procured locally and administered in men and premenopausal women as an injectable subcutaneous implant administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 3.6 mg (cycle = 28 days)
LeuprolideDRUGLeuprolide was procured locally and administered in men and premenopausal women as an injectable intramuscular depot administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 7.5 mg (cycle= 28 days)
AnastrozoleDRUGAnastrozole 1 mg tablets for oral use QD continuously
Docetaxel / CapecitabineCOMBINATION_PRODUCTDocetaxel (IV Infusion) / Capecitabine (Tablets for oral use): Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day)
Capecitabine / VinorelbineCOMBINATION_PRODUCTCapecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ). Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles. Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day \[oral\] or (25 to 30 mg/m2 \[IV infusion\]
Paclitaxel / GemcitabineCOMBINATION_PRODUCTPaclitaxel (IV Infusion) / Gemcitabine (IV Infusion): Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (IV) infusion on Day 1 and day 8- in 3-weeks cycles. Gemcitabine at via 30 minute IV infusion on Day 1 and Day 8 in 3 weeks cycles. Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2) OR Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2)
Letrozole OR AnastrozoleDRUGLetrozole: Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use Anastrozole: dose: 1 mg All days of every cycle without interruption. Tablets for oral use The NSAI (letrozole or anastrozole) will be decided by the treating physician.
Ribociclib PlaceboDRUGFilm-coated tablets for oral use (200 mg x 3) from days 1 to 21 of each 28 day cycle.
NSAI: Letrozole or AnastrazoleDRUGLetrozole: Tablets for oral use, 2.5mg daily (all days of every cycle without interruption). Anastrazole: Tablets for oral use, 1mg daily (all days of every cycle without interruption) For Premenopausal cohort, it is the investigators choice for NSAI based on patients past history. For postmenopausal and PK cohorts, all patients will be on Letrozole.
Adjuvant endocrine therapyDRUGLetrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.
PlaceboDRUGPlacebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Placebo was supplied in the form of 200 mg film-coated tablets taken by mouth.
LEE011DRUGSingle agent LEE011 or in combination with other treatments
LEE011 PlaceboDRUG -
T-DM1DRUG -
TrastuzumabDRUG -
FulvestrantDRUG -
EverolimusDRUGTreatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.
Combination of ribociclib + capecitabineDRUGRIBOCICLIB from 200 to 600mg once daily + CAPECITABINE from 750 to 1000 mg/m² BID, cycles are defined in 21-day periods, 2 weeks on treatment, 1 week off treatment
ExemestaneDRUGsupplied in 25 mg tablets taken orally, daily for 28 day cycle
TamoxifenDRUG20 mg
BuparlisibDRUGdaily
BYL719DRUGBYL719: supplied as tablets of dosage strength of 10 mg, 50 mg or 200 mg. Tablets will be differentiated through different sizes and/or colors.
BKM120DRUGBKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.
ribociclib (LEE011)DRUGLEE011 is taken orally once per day for 21 days of each 28 day cycle. LEE011 comes in 50 mg and 200 mg capsules.
Everolimus (RAD001)DRUGEverolimus is taken orally once per day. Everolimus comes in 1 mg, 2.5 mg, 5mg, and 7.5 mg tablets
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Eligibility Criteria

Age Range18 Years to N/A
SexFEMALE
Healthy VolunteersNo
Study Sites27

Inclusion Criteria: * Age ≥ 18 years. * Any menopausal status. If pre-/perimenopausal, agreement to receive LHRH agonist (goserelin or leuprorelin) / ovarian ablation in case of randomization to arm A * Locally confirmed diagnosis of metastatic adenocarcinoma of the breast without prior systemic an...

Countries:GermanyUnited StatesArgentinaAustriaBelgiumBulgariaCanadaChileCzechiaDenmarkFinlandFranceGreeceHong KongHungaryIndiaIsraelItalyJordanLebanonMalaysiaMexicoNetherlandsNorwayOmanPanamaPhilippinesPolandPortugalRussiaSaudi ArabiaSingaporeSlovakiaSloveniaSpainSwedenTaiwanThailandUnited KingdomBrazilColombiaCosta RicaLithuaniaPeruSouth AfricaEgyptTurkey (Türkiye)VietnamChinaJapanSouth KoreaAustraliaSwitzerland
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Competitive Landscape -Breast Cancer 402 trials

Top 20 of 92 competitors

CompanyTickerTrialsLead PhaseDrugs
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant
BeOne Medicines Ltd. Sponsored ADRONC5PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib
Relay Therapeutics, Inc.RLAY2PHASE3Zovegalisib, Capivasertib, Fulvestrant
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam
Atossa Therapeutics, Inc.ATOS1PHASE2endoxifen, goserelin
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Recent Changes (Last 90 Days)

MEDIUMAug 8, 2026NCT03671330TRIAL_REMOVED: changed
MEDIUMAug 8, 2026NCT03671330TRIAL_REMOVED: changed
MEDIUMAug 8, 2026NCT03671330TRIAL_REMOVED: changed
MEDIUMAug 8, 2026NCT03671330TRIAL_REMOVED: changed
LOWJun 11, 2026NCT01872260lastUpdatePostDate: changed
LOWJun 11, 2026NCT01872260lastUpdatePostDate: changed

Frequently asked questions about LEE011

What is LEE011 (ribociclib) used for?

LEE011, also known as ribociclib, is an investigational small molecule being studied for multiple oncology indications, including early breast cancer, hormone receptor positive HER2-negative breast cancer, advanced breast cancer, and glioblastoma multiforme. It is currently in Phase 1 clinical development.

What does LEE011 (ribociclib) target?

LEE011 (ribociclib) is a cyclin-dependent kinase (CDK) inhibitor, belonging to the -ciclib class of drugs that target CDK enzymes involved in cell cycle regulation. It is being evaluated for its role in treating various cancers, including breast cancer and glioblastoma multiforme.

Who makes LEE011 (ribociclib)?

LEE011 (ribociclib) is developed by Novartis AG, a global pharmaceutical company listed on the stock exchange under the ticker symbol NVS. The drug is being investigated in clinical trials for multiple cancer indications.

What phase is LEE011 (ribociclib) in?

LEE011 (ribociclib) is currently in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug has received a rare pediatric disease designation from the FDA.

What clinical trials is LEE011 (ribociclib) in?

LEE011 (ribociclib) has been studied in 12 clinical trials with a total enrollment of 6,501 participants. Notable trials include NCT03701334, a Phase 3 study in early breast cancer with 5,101 patients, and NCT05827081, a Phase 3b study in early breast cancer currently recruiting.

Is LEE011 the same as ribociclib?

Yes, LEE011 is also known as ribociclib. The drug is referred to by both names in clinical research, and it is being developed by Novartis AG for the treatment of various cancers, including breast cancer and glioblastoma multiforme.