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Ribociclib (LEE011)

Alias: LEE 011; Ribociclib; LEE011; LEE-011; trade name: Kisqali; Ribociclib (LEE011); LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;
Cat No.:V1550 Purity: ≥98%
Ribociclib (formerly NVP-LEE011; LEE011; LEE-011; trade name:Kisqali) is a potent, orally bioavailable and highly specific inhibitor of CDK4/6 (cyclin-dependent kinase) with potential antineoplastic activity.
Ribociclib (LEE011)
Ribociclib (LEE011) Chemical Structure CAS No.: 1211441-98-3
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
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10mg
25mg
50mg
100mg
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1g
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Other Forms of Ribociclib (LEE011):

  • Ribociclib HYDROCHLORIDE
  • Ribociclib-d6 hydrochloride (LEE011-d6 (hydrochloride))
  • RIBOCICLIB SUCCINATE (LEE011)
  • RIBOCICLIB SUCCINATE HYDRATE
  • Ribociclib-d6 (LEE011-d6)
  • Ribociclib-d8 (LEE011-d8)
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Ribociclib (formerly NVP-LEE011; LEE011; LEE-011; trade name: Kisqali) is a potent, orally bioavailable and highly specific inhibitor of CDK4/6 (cyclin-dependent kinase) with potential antineoplastic activity. Its IC50s for CDK4/6 inhibition are 10 nM and 39 nM, respectively. In March 2017, the FDA approved Ribociclib as a treatment for postmenopausal women who had an advanced form of breast cancer. Ribociclib works by reducing the levels of phosphorylated FOXM1 and RB. Out of 17 human neuroblastoma cell lines tested, 12 showed sensitivity to Ribociclib treatment (mean IC50=306±68 NM). By stopping the G0-G1 cell cycle, ribociclib treatment may significantly reduce the rate of cell proliferation. Treatment with LEE011 could markedly inhibit cell proliferation in 12 out of 17 human neuroblastoma-derived cell lines.

Biological Activity I Assay Protocols (From Reference)
Targets
CDK4 (IC50 = 10 nM); CDK6 (IC50 = 39 nM)
ln Vitro
Treating a panel of 17 neuroblastoma cell lines with Ribociclib (LEE011) across a four-log dose range (10 to 10,000 nM). In 12 of the 17 neuroblastoma cell lines that were studied, treatment with ribociclib dramatically reduces substrate adherent growth in comparison to the control (mean IC50=306±68 nM, taking only sensitive lines into consideration; sensitivity is defined as an IC50 of less than 1 μM). After being treated with ribofloxacilb, two neuroblastoma cell lines (IMR5 and BE2C) that have been shown to be sensitive to CDK4/6 inhibition accumulate cells in the G0/G1 phase of the cell cycle in a dose-dependent manner. At concentrations of 100 nM (p=0.007) and 250 nM (p=0.01), respectively, of Ribociclib, this G0/G1 arrest becomes significant[2].
ln Vivo
Ribociclib (LEE011; 200 mg/kg) or a vehicle control is administered once daily for 21 days to CB17 immunodeficient mice carrying BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts. Since none of the xenograft models exhibit weight loss or other toxicity indicators, this dosage strategy is well tolerated. During the course of the 21-day treatment period, mice carrying either the BE2C or 1643 xenografts (both, p<0.0001) showed a significant delay in tumor growth, which did not resume after treatment[2].
CDK4/6 inhibition by Ribociclib (LEE011) causes tumor growth delay in vivo [2]
Given the observed differential sensitivity of neuroblastoma cell lines to CDK4/6 inhibition, we assayed for in vivo efficacy using neuroblastoma cell-line derived xenografts representing the extremes of in vitro sensitivity. CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts were treated once daily for 21 days with Ribociclib (LEE011) or with a vehicle control. This dosing strategy was well tolerated, as no weight loss or other signs of toxicity were observed in any of the xenograft models. As shown in Figures 5A and S6, tumor growth was significantly delayed throughout the 21 days of treatment in mice harboring the BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment (data not shown). By contrast, as anticipated by the in vitro data, tumor growth suppression was less robust in the EBC1 xenograft model (p=0.51). Assessment of the Ki67 proliferation marker by immunohistochemistry confirmed that proliferation was impaired only in the BE2C and 1643 xenograft models, as tumors resected from separate cohorts of BE2C or 1643 xenografted mice demonstrated comparatively weaker staining following 7 days of treatment with Ribociclib (LEE011) than with the vehicle control, while no Ki67 staining differences were observed in the EBC1 xenografts (Figure 5B). Phosphorylation of RB was also substantially diminished in the BE2C and 1643 xenografts, while only a minimal decrease was detected in the EBC1 model (Figures 5B and 5C) [2].
Enzyme Assay
Ribociclib, a powerful, oral, and highly selective inhibitor of CDK4/6 (cyclin-dependent kinase), with IC50s of 10 nM and 39 nM, respectively, was previously known as LEE011, NVP-LEE011; trade name: Kisqali. In March 2017, the FDA approved Ribociclib as a treatment for postmenopausal women who had an advanced form of breast cancer. Ribociclib works by reducing the levels of phosphorylated FOXM1 and RB. Out of 17 human neuroblastoma cell lines tested, 12 showed sensitivity to ribofacilb treatment (mean IC50=306±68 NM). By stopping the G0-G1 cell cycle, ribociclib treatment may significantly reduce the rate of cell proliferation. Treatment with LEE011 could markedly inhibit cell proliferation in 12 out of 17 human neuroblastoma-derived cell lines.
Cell Assay
In 35 mm plates, cells are grown for 24 hours, then treated with 500 nM Ribociclib for 6 days. The cells are then fixed, and overnight staining is done. Then, using an Axio Observer D.1 phase contrast microscope, cells are imaged for SA-β-gal. By counting the number of positive cells in three different microscope frames and normalizing to the control, one can calculate the percentage of SA-β-gal positive cells. In order to evaluate apoptotic activity, cells are treated with Ribociclib, plated in triplicate in 96-well plates, and then 16 hours later, caspase 3/7 activation is measured 16 hours after Caspase-Glo 3/7 treatment. As a positive control, SN-38-treated cells are employed[2].
Animal Protocol
Mice: The xenografts derived from BE2C, NB-1643, or EBC1 cell lines are subcutaneously implanted into the right flank of CB17 SCID-/-mice. Then, for a total of 21 days, animals with engrafted tumors measuring 200–600 mm3 are randomly assigned to receive oral treatment with 200 mg/kg Ribociclib in 0.5% methylcellulose (n = 10) or vehicle (n = 10). Throughout the course of treatment, the tumor burden is calculated on a regular basis using the formula (π/6)×d2, where d is the mean tumor diameter measured with a caliper.
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Ribociclib is orally bioavailable, highly selective inhibitor of CDK4/6 kinases with inhibitory IC50 concentrations in the low nanomolar range. Following oral dosing, ribociclib was rapidly absorbed with median Tmax ranging from 1 to 5 hours. Plasma concentrations increased approximately 2- to 3-fold from Cycle 1 Day 1 to Cycle 1 Day 18/21 due to accumulation, with steady state reached by approximately Day 8 on the basis of trough concentrations after repeated daily dosing. Dose-proportionality analyses demonstrated that exposure to ribociclib increased with dose, with both Cmax and area under the curve (AUC) increasing slightly more than proportional to dose, over the dose range 50–1,200 mg/day
Biological Half-Life
32.6 hours
Toxicity/Toxicokinetics
Hepatotoxicity
In the large clinical trials, adverse events were common and led to dose reductions in 45% of patients and discontinuation in 7%. In preregistration clinical trials, ALT elevations occurred in 46% of ribociclib vs 36% of control subjects and elevations above 5 times the ULN in 10% vs 1%. In one study, 1% of recipients developed clinically apparent liver injury with jaundice, but all recovered. The liver injury arose after 3 to 5 cycles and presented with asymptomatic elevations in serum ALT followed by symptoms and jaundice. Immunoallergic and autoimmune features were not present, although liver histology sometimes showed autoimmune hepatitis-like features. Recovery was slow (3 to 5 months), but ultimately complete. Restarting ribociclib resulted in more rapid and severe recurrence. Thus, experience with ribociclib is limited, but it appears to be capable of causing significant liver injury.
Likelihood score: C (probable cause of clinically apparent liver injury).
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of ribociclib during breastfeeding. Because protein binding of ribociclib is 70%, clinically important amounts of the drug might pass into breastmilk. The manufacturer recommends that breastfeeding be discontinued during ribociclib therapy and for at least 3 weeks after the final dose.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
References

[1]. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10.

[2]. Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.

Additional Infomation
Ribociclib is a member of piperazines and a member of pyridines.
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. Ribociclib was approved by the U.S. FDA in March, 2017 as Kisqali.
Ribociclib is a Kinase Inhibitor. The mechanism of action of ribociclib is as a Kinase Inhibitor, and Cytochrome P450 3A Inhibitor.
Ribociclib is a unique cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Ribociclib is associated with a moderate rate of serum aminotransferase elevations during therapy, and to clinically apparent liver injury in a proportion of these.
Ribociclib is an orally available cyclin-dependent kinase (CDK) inhibitor targets at cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. Ribociclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
See also: Ribociclib Succinate (active moiety of).
Drug Indication
Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
Kisqali is indicated for the treatment of women with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre‑ or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone‑releasing hormone (LHRH) agonist.
Treatment of neuroblastoma
Mechanism of Action
Inhibition of cyclin-dependent kinase 4 and 6 (CDK4/6) may provide protection against oncogenic processes in specific tissue types. For example, CDK4 is not required for normal mammary tissue development based on knockout mouse studies, but it is needed for growth of Ras-induced mammary tumors, suggesting a potential therapeutic window for treatment with lower toxicity. Ribociclib was reported to be a most selective CDK4/6 inhibitor and to have dose dependent antitumor activity in a number of preclinical models. It inhibited growth of tumor cells by arresting the cells at the G1 checkpoint, which prevents the tumor cells from proliferating.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C23H30N8O
Molecular Weight
434.54
Exact Mass
434.254
Elemental Analysis
C, 63.57; H, 6.96; N, 25.79; O, 3.68
CAS #
1211441-98-3
Related CAS #
Ribociclib hydrochloride;1211443-80-9;Ribociclib-d6 hydrochloride;Ribociclib succinate;1374639-75-4;Ribociclib succinate hydrate;1374639-79-8;Ribociclib-d6;1328934-40-2;Ribociclib-d8;2167898-24-8
PubChem CID
44631912
Appearance
Yellow solid powder
Density
1.4±0.1 g/cm3
Boiling Point
730.8±70.0 °C at 760 mmHg
Flash Point
395.8±35.7 °C
Vapour Pressure
0.0±2.4 mmHg at 25°C
Index of Refraction
1.723
LogP
-0.74
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
5
Heavy Atom Count
32
Complexity
636
Defined Atom Stereocenter Count
0
SMILES
N1(CCNCC1)C1C=NC(NC2N=C3N(C(C(N(C)C)=O)=CC3=CN=2)C2CCCC2)=CC=1
InChi Key
RHXHGRAEPCAFML-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H30N8O/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)
Chemical Name
7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
Synonyms
LEE 011; Ribociclib; LEE011; LEE-011; trade name: Kisqali; Ribociclib (LEE011); LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~7 mg/mL (~16.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 1 mg/mL (2.30 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 1 mg/mL (2.30 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.89 mg/mL (2.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.9 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.


Solubility in Formulation 4: ≥ 0.89 mg/mL (2.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.9 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 5: ≥ 0.89 mg/mL (2.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.9 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 6: 5% DMSO+40% PEG 300+5%Tween80+ 50%ddH2O: 1.1mg/ml

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.3013 mL 11.5064 mL 23.0128 mL
5 mM 0.4603 mL 2.3013 mL 4.6026 mL
10 mM 0.2301 mL 1.1506 mL 2.3013 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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In vivo Formulation Calculator (Clear solution)
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Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Clinical Trial Information
The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
CTID: NCT06377852
Phase: Phase 3    Status: Recruiting
Date: 2024-11-29
Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer
CTID: NCT05467891
Phase: Phase 2    Status: Recruiting
Date: 2024-11-27
Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
CTID: NCT01872260
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-11-27
Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer
CTID: NCT03822468
Phase: Phase 2    Status: Completed
Date: 2024-11-27
Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-based Cohorts
CTID: NCT04657679
Phase: Phase 4    Status: Terminated
Date: 2024-11-26
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First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
CTID: NCT05768139
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-25


TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)
CTID: NCT05573555
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-22
Phase Ib Study of TNO155 in Combination With Spartalizumab or Ribociclib in Selected Malignancies
CTID: NCT04000529
Phase: Phase 1    Status: Terminated
Date: 2024-11-22
Ribociclib in Combination With Adjuvant Endocrine Therapy for Patients With Early High-risk HR+HER2- Breast Cancer
CTID: NCT06587789
Phase:    Status: Recruiting
Date: 2024-11-21
Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer
CTID: NCT06380751
Phase: Phase 3    Status: Recruiting
Date: 2024-11-19
Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer
CTID: NCT05563220
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-18
Study of Efficacy and Safety of Ribociclib (LEE011) in Combination With Topotecan and Temozolomide (TOTEM) in Pediatric Patients With Relapsed or Refractory Neuroblastoma and Other Solid Tumors
CTID: NCT05429502
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-15
A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)
CTID: NCT06065748
Phase: Phase 3    Status: Recruiting
Date: 2024-11-15
Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
CTID: NCT04417621
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-11-15
Phase IIIb Study of Ribociclib + ET in Early Breast Cancer
CTID: NCT05827081
Phase: Phase 3    Status: Not yet recruiting
Date: 2024-11-15
Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
CTID: NCT05358249
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-11-15
A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer
CTID: NCT03701334
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-11-14
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
CTID: NCT03424005
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-13
Adj. Marker-adjusted Personalized Therapy Comparing ET+Ribociclib vs Chemotherapy in Intermediate Risk, HR+/HER2- EBC
CTID: NCT04055493
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-11-12
Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
CTID: NCT04862663
Phase: Phase 3    Status: Recruiting
Date: 2024-11-08
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
CTID: NCT04802759
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-11-06
Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics
CTID: NCT04315233
Phase: Phase 1    Status: Recruiting
Date: 2024-10-30
Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL
CTID: NCT03740334
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-10-24
Study of Ribociclib and Everolimus in HGG and DIPG
CTID: NCT05843253
Phase: Phase 2    Status: Recruiting
Date: 2024-10-21
A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/characteristics in Advanced / Metastatic Tumors.
CTID: NCT04116541
Phase: Phase 2    Status: Recruiting
Date: 2024-10-16
Roll-over Study to Allow Continued Access to Ribociclib
CTID: NCT05161195
Phase: Phase 4    Status: Recruiting
Date: 2024-10-15
Ribociclib and Bicalutamide in AR+ TNBC
CTID: NCT03090165
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-10-15
Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.
CTID: NCT03671330
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-10-10
A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors
CTID: NCT03070301
Phase: Phase 2    Status: Completed
Date: 2024-10-10
Study to Compare the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Combination Chemotherapy in Premenopausal or Perimenopausal Patients With Advanced or Metastatic Breast Cancer
CTID: NCT03839823
Phase: Phase 2    Status: Completed
Date: 2024-10-09
A First-in-human Dose Escalation and Expansion Study to Evaluate the Safety, and Tolerability of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors
CTID: NCT06188520
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-10-03
Phase 1b Combo w/ Ribociclib, Alpelisib, or Everolimus
CTID: NCT05508906
Phase: Phase 1    Status: Recruiting
Date: 2024-10-03
Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, Node Positive, HR+/HER2- Breast Cancer
CTID: NCT05996107
Phase: Phase 1    Status: Suspended
Date: 2024-10-02
Sequential Therapies Modeled on Evolutionary Dynamics for Breast Cancer
CTID: NCT06409390
PhaseEarly Phase 1    Status: Recruiting
Date: 2024-10-01
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
CTID: NCT04964934
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-09-27
FACILE: FeAsibility of First-line riboCIclib in oLdEr Patients With Advanced Breast Cancer
CTID: NCT03944434
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-09-25
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, As a Single Agent in Advanced Solid Tumor Patients and in Combination with Fulvestrant in Patients with Advanced Breast Cancer
CTID: NCT05216432
Phase: Phase 1    Status: Recruiting
Date: 2024-09-23
Study to Determine the Safety and Efficacy of Ribociclib in Combination With Hormone Therapy and Hypofractionated Radiotherapy in Breast Cancer, With Positive Hormone Receptors and Negative HER2 Status, in Newly Diagnosed, Not Immediately Operable Elderly Patient (CALHYS)
CTID: NCT05664893
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-09-23
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
CTID: NCT03333343
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-09-19
[18F]FLT PET/CT in Rb+ Metastatic Breast Cancer
CTID: NCT02608216
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-08-28
Phase 1b/2 Study of TTI-101 in Combination for Patients With Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer
CTID: NCT05384119
Phase: Phase 1/Phase 2    Status: Completed
Date: 2024-08-22
A Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma
CTID: NCT03008408
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-08-15
A Phase IV Study to Collect Data on the Efficacy and Safety of RIBociclib in Older Women With Breastcancer
CTID: NCT03956654
Phase:    Status: Completed
Date: 2024-08-09
A Phase 0 /II Study of Ribociclib (LEE011) in Combination With Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection
CTID: NCT03834740
PhaseEarly Phase 1    Status: Completed
Date: 2024-08-05
Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant
CTID: NCT03439046
Phase: Phase 3    Status: Completed
Date: 2024-08-01
[177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer
CTID: NCT05870579
Phase: Phase 1    Status: Recruiting
Date: 2024-07-18
Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)
CTID: NCT03114527
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-07-12
A Real-life Study to Understand the Use and Effects of Palbociclib in US Patients With Breast Cancer
CTID: NCT06495164
Phase:    Status: Active, not recruiting
Date: 2024-07-10
T-DM1 Combined With CDK4/6 Inhibitor Ribociclib
CTID: NCT06481956
Phase: Phase 2    Status: Enrolling by invitation
Date: 2024-07-01
Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclib
CTID: NCT05625087
Phase: Phase 2    Status: Recruiting
Date: 2024-06-24
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic
A Phase Ib/III Randomised Study of Capivasertib plus CDK4/6i and Fulvestrant versus Placebo plus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer
CTID: null
Phase: Phase 1, Phase 3    Status: Trial now transitioned, Ongoing
Date: 2021-07-14
A randomized, open-label, multi-arm, two-part, phase II study to assess the efficacy and safety of multiple LXH254 combinations in patients with previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma
CTID: null
Phase: Phase 2    Status: Ongoing, Trial now transitioned, GB - no longer in EU/EEA, Completed
Date: 2020-11-02
Ribociclib-endocrine combination therapy versus chemotherapy as 1st line treatment in patients with visceral metastatic breast cancer.
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2020-02-26
Phase II, multicenter, single arm trial to assess the feasibility of first line ribociclib in combination with a non steroidal aromatase inhibitor in elderly patients with hormone receptor positive/HER2 negative advanced breast cancer
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2019-11-12
MegaMOST - A multicenter, open-label, biology driven, Phase II study evaluating the activity of anti-cancer treatments targeting tumor molecular alterations/characteristics in advanced / metastatic tumors.
CTID: null
Phase: Phase 2    Status: Trial now transitioned
Date: 2019-08-03
A phase II, multicenter, randomized, open-label study to evaluate the safety and efficacy of 400 mg of ribociclib in combination with non-steroidal aromatase inhibitors for the treatment of pre- and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received no prior therapy for advanced disease.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2019-05-24
A phase III, multicenter, randomized, open-label trial toevaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer (New Adjuvant TriAl with Ribociclib [LEE011]: NATALEE)
CTID: null
Phase: Phase 3    Status: Trial now transitioned, Ongoing, GB - no longer in EU/EEA
Date: 2019-02-25
A randomized, open-label, phase II open platform study evaluating the efficacy and safety of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma
CTID: null
Phase: Phase 2    Status: Ongoing, GB - no longer in EU/EEA, Prematurely Ended
Date: 2018-10-19
A randomized, open-label, multicenter, two-arm, phase III study to evaluate efficacy and quality of life in patients with metastatic hormone receptor-positive HER2-negative breast cancer receiving ribociclib in combination with endocrine therapy or chemotherapy with or without bevacizumab in first line
CTID: null
Phase: Phase 3    Status: Completed
Date: 2018-02-14
Tailoring neoadjuvant therapy in hormone receptor positive, HER2 negative, luminal breast cancer.
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2018-01-12
A phase IIIb, open-label, local, multicenter study of the molecular features of postmenopausal women with hormone receptor-positive (HR+) HER2-negative advanced breast cancer on first-line treatment with ribociclib and letrozole (BioItaLEE)
CTID: null
Phase: Phase 3    Status: Prematurely Ended
Date: 2018-01-10
Anti-hormonal maintenance treatment with the CDK4/6 inhibitor Ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial
CTID: null
Phase: Phase 2    Status: Completed
Date: 2017-12-29
A phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, high risk early breast cancer
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2017-11-02
Selecting the Optimal position of CDK4/6 Inhibitors in HR+ Advanced breast cancer: the SONIA trial
CTID: null
Phase: Phase 3    Status: Ongoing
Date: 2017-09-29
CORALLEEN: A Phase 2 Clinical Trial of multi-agent Chemotherapy or letrozole plus Ribociclib (LEE001) as neoadjuvant treatment for postmenopausal patients with Luminal B/HER2-negative breast cancer.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2017-03-29
COMPLEEMENT-1: An open-label, multicenter, Phase IIIb study to assess the safety and efficacy of ribociclib (LEE011) in combination with letrozole for the treatment of men and pre / postmenopausal women with hormone receptorpositive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced disease
CTID: null
Phase: Phase 3    Status: Ongoing, GB - no longer in EU/EEA, Completed
Date: 2016-12-08
An open-label, multi-center rollover protocol for patients who have participated in a Novartis-sponsored ribociclib (LEE011) study and are continuing to benefit from ribociclib as single agent or in combination with other investigational treatments
CTID: null
Phase: Phase 2    Status: Ongoing, Completed
Date: 2016-12-05
A national phase IIIb, multi-center, open label study for women and men with hormone-receptor positive, HER2-negative locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole
CTID: null
Phase: Phase 3    Status: Completed
Date: 2016-10-14
European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumours
CTID: null
Phase: Phase 1, Phase 2    Status: Trial now transitioned, Ongoing, GB - no longer in EU/EEA
Date: 2016-05-25
A phase I/II study of safety and efficacy of ribociclib (LEE011) in combination with trametinib (TMT212) in patients with metastatic or advanced solid tumors
CTID: null
Phase: Phase 1, Phase 2    Status: Prematurely Ended
Date: 2016-05-24
DETECT V/CHEVENDO: A multicenter, randomized phase III study to compare chemo- versus endocrine therapy in combination with dual HER2-targeted therapy of Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus Kisqali® (ribociclib) in patients with HER2 positive and hormone-receptor positive metastatic breast cancer.
CTID: null
Phase: Phase 3    Status: Ongoing
Date: 2015-07-15
MONALEESA-3: A randomized double-blind, placebo-controlled study of ribociclib in combination with fulvestrant for the treatment of men and postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who have received no or only one line of prior endocrine treatment
CTID: null
Phase: Phase 3    Status: Completed
Date: 2015-05-27
A Phase Ib/II, open-label, multicenter study of oral HDM201 in combination with oral LEE011 in adult patients with liposarcoma
CTID: null
Phase: Phase 1, Phase 2    Status: Prematurely Ended, Completed
Date: 2015-05-11
A phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive Non-small Cell Lung Cancer
CTID: null
Phase: Phase 1, Phase 2    Status: Prematurely Ended, Completed
Date: 2014-12-26
A Phase III randomized, double-blind, placebo-controlled study of LEE011 or placebo in combination with tamoxifen and goserelin or a non-steroidal aromatase inhibitor (NSAI) and goserelin for the treatment of premenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer
CTID: null
Phase: Phase 3    Status: Ongoing, Completed
Date: 2014-12-19
A randomized, blinded, placebo-controlled, phase II trial of LEE011 in patients with relapsed, refractory, incurable teratoma with recent progression
CTID: null
Phase: Phase 2    Status: Temporarily Halted, Prematurely Ended, Completed
Date: 2014-10-24
A phase Ib/II study of LEE011 in combination with fulvestrant and BYL719 or BKM120 in the treatment of postmenopausal women with hormone receptor positive, HER2 negative locally recurrent or advanced metastatic breast cancer
CTID: null
Phase: Phase 1, Phase 2    Status: Prematurely Ended
Date: 2014-04-17
A randomized double-blind, placebo-controlled study of LEE011 in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease
CTID: null
Phase: Phase 3    Status: Completed
Date: 2014-01-24
A randomized pre-surgical pharmacodynamics study to assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer
CTID: null
Phase: Phase 2    Status: Prematurely Ended, Completed
Date: 2013-12-30
A multicenter phase II study in patients with HER2-negative metastatic breast cancer and persisting HER2-negative circulating tumor cells (CTCs).
CTID: null
Phase: Phase 2    Status: Completed
Date: 2013-12-19
A phase Ib/II, multicenter, study of LEE011 in combination with LGX818 in adult patients with BRAF mutant melanoma
CTID: null
Phase: Phase 1, Phase 2    Status: Completed, Prematurely Ended
Date: 2013-12-03
A phase Ib/II, multicenter, study of the combination of LEE011 and BYL719 with letrozole in adult patients with advanced ER+ breast cancer
CTID: null
Phase: Phase 1, Phase 2    Status: GB - no longer in EU/EEA, Trial now transitioned, Temporarily Halted, Completed
Date: 2013-11-12
Phase II, Multi-center, Open-label Study of Single-agent LGX818 Followed by a Rational Combination With Agents After Progression on LGX818, in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma
CTID: null
Phase: Phase 2    Status: Completed, Prematurely Ended
Date: 2013-10-12
A phase Ib/II trial of LEE011 in combination with everolimus (RAD001) and exemestane in the treatment of postmenopausal women with estrogen receptor positive Her2 negative locally advanced or metastatic breast cancer
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2013-10-12
A phase IB/II, multicenter, open label, study of LEE011 in combination with MEK162 in adult patients with NRAS mutant melanoma
CTID: null
Phase: Phase 1, Phase 2    Status: Completed
Date: 2013-07-11
A phase I, multi-center, open-label study of LEE011 in patients with malignant rhabdoid tumors and neuroblastoma
CTID: null
Phase: Phase 1    Status: Completed, Prematurely Ended
Date: 2013-04-22
A Phase Ib/II, multicenter, open-label, dose escalation study of LGX818 in combination with MEK162 in adult patients with BRAF V600 - dependent advanced solid tumors
CTID: null
Phase: Phase 1, Phase 2    Status: Ongoing, Completed
Date: 2012-05-30

Biological Data
  • Ribociclib (LEE011)


    Pharmacologic inhibition of CDK4/6 suppresses neuroblastoma growthin vitro.(A)The growth of 12 of 17 neuroblastoma cell lines was significantly impaired in response to CDK4/6 inhibition with LEE011 (mean IC50= 306 ± 68 nM, sensitive lines only). Data are plotted (and tabulated) as the best fit IC50per log(inhibitor) vs. normalized response analysis (GraphPad); upper and lower bars represent 95 % confidence levels.(B)Dose-dependent decreases in pRBS780accompany growth suppression in sensitive lines and are indicative of on- target activity.2013 Nov 15;19(22):6173-82.

  • Ribociclib (LEE011)


    Growth suppression via CDK4/6 inhibition is mediated by cell cycle arrest and senescence. Neuroblastoma cell lines with demonstrated sensitivity or resistance to LEE011 were analyzed for cell cycle arrest and senescence associated β-galactosidase (SA-β-gal) activity.(A)A significant G1arrest accompanied by reductions in the fraction of cells in S phase and G2/M was observed in sensitive lines only.(B)Representative cell cycle histograms of a sensitive and resistant cell line.(C)Down-regulation of FOXM1 mRNA and(D)protein was observed in sensitive lines and was associated with(E)the induction of a senescent phenotype.2013 Nov 15;19(22):6173-82.

  • Ribociclib (LEE011)


    Inhibition of CDK4/6 suppresses neuroblastoma growthin vivo.(A)Mice with subcutaneously implanted xenografts were treated daily with 200 mg/kg LEE011 or with a vehicle for 21 days. In two of three neuroblastoma xenograft models, treatment with LEE011 significantly reduced tumor burden in comparison to vehicle, as determined by linear mixed effects analysis (BE2C, p<0.0001; 1643, p <0.0001; EBC1 p = 0.51).(B)The reduction in tumor proliferation observed in sensitive lines was confirmed by Ki67 staining of resected xenografts, and inhibition of CDK4/6 activity was confirmed by(C)immunohistochemical staining and western blot for pRBS780.2013 Nov 15;19(22):6173-82.

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