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Ribociclib+ Letrozole OR Fulvestrant

Phase 3

Metastatic Breast Cancer | Small molecule | Oncology |Novartis AG|Last Updated: Apr 29, 2025

Target and mechanism

Molecular targetCDK6, CDK4
Target classInhibitor
ModalitySmall molecule

Also known as Ribociclib, LEE011, ribociclib, Ribociclib (neoadjuvant)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment659

FDA Designations

RARE_PEDIATRIC_DISEASE

Clinical trial landscape

Ribociclib+ Letrozole OR Fulvestrant · 3 trials · 3 indications

Phase 3 1Phase 2 1Phase 1 1
NCT05207709Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic SubtypeMetastatic Breast Cancer
ACTIVE NOT_RECRUITING456 Analytics
PHASE3ACTIVE NOT_RECRUITING
Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
Metastatic Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression-free survival
From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled

using RECIST 1.1 criteria, as assessed by local radiologists/investigators

Progression Free Survival (PFS)
Up to approximately 30 months

Progression free survival (PFS) is defined as the interval from the time of randomization until objective disease progression (local assessment) or death from any cause. Disease status will be assessed with comprehensive radiographic studies every three treatment cycles (approximately every 12 weeks (+/- 1 week)). Disease progression as assed by RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

MTD of ribociclib and belinostat combination
C1D1 to C2D1 (each cycle is 28 days)

incidence of DLTs during the defined DLT period

Secondary Endpoints

Progression-free survival 2
From randomization until documented progression to second line of therapy, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled
Overall Survival
until patient death, assessed up to approximately 62 months after the first patient enrolled
Overall response and clinical benefit
until disease progression or 24 weeks from treatment start.
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Ribociclib + Endocrine TherapyEXPERIMENTALRibociclib + Fulvestrant or Letrozole
Palbociclib + Endocrine TherapyEXPERIMENTALPalbociclib + Fulvestrant or Letrozole
Paclitaxel +/- Tislelizumab - Exploratory cohortEXPERIMENTALAdditional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Ribociclib (LEE-011)/FulvestrantEXPERIMENTALLEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Placebo/FulvestrantPLACEBO_COMPARATORPlacebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Cohort 1: Dose Escalation CohortEXPERIMENTALRibociclib and belinostat will be given at escalating doses and on multiple administration schedules throughout the dose escalation component of the study. The MTD identified in the dose escalation component will be used to define the dose and administration schedule used in the dose expansion.
Cohort 2: Dose expansion cohortEXPERIMENTALParticipant will be enrolled in dose expansion cohort at the identified Recommended Phase 2 Dose (RP2D). Dose escalation will be open to the enrollment of patients diagnosed with triple-negative breast cancer or ovarian cancer. However, dose expansion will only be open to the enrollment of patients diagnosed with triple-negative breast cancer

Interventions

NameTypeDescription
Ribociclib + Letrozole OR FulvestrantDRUGEndocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Palbociclib + Letrozole OR FulvestrantDRUGEndocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Paclitaxel +/- TislelizumabDRUGPatients in this arm could receive as the first line of therapy
LEE-011DRUG600 mg capsule (3x 200 mg capsules)
FulvestrantDRUG500 mg injection
PlaceboDRUG600 mg capsule (3x 200 mg capsules)
RibociclibDRUGRibociclib Dose Level 0 (starting dose) 200mg QD Dose Level 1A 400mg QD on Days 8-28 Dose Level 1B 200mg QD Dose Level 2 400mg QD on Days 8-28
BelinostatDRUGBelinostat Dose Level 0 (starting dose) 600mg/m2 daily for 5 days Dose Level 1A 600mg/m2 daily for 5 days Dose Level 1B 1000mg/m2 daily for 5 days Dose Level 2 1000mg/m2 daily for 5 days \*Administration on 5 consecutive days is preferred. Administration within 7 days allowed as needed to accommodate holidays and infusion schedules.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites71

Main Inclusion Criteria: * Histologically documented HR-positive and HER2-negative breast cancer by local testing * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer. * Availabi...

Countries:United StatesPortugalSpain
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Competitive Landscape -Breast Cancer 402 trials (matched to "Metastatic Breast Cancer")

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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Frequently asked questions about Ribociclib+ Letrozole OR Fulvestrant

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.