Details of the Drug Combinations

General Information of This Drug (ID: DMMX75K)

• Drug Name: LEE011 (DMMX75K)
• Synonyms: Ribociclib; LEE011; 1211441-98-3; LEE-011; Kisqali; Ribociclib(LEE011); UNII-TK8ERE8P56; LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; TK8ERE8P56; Ribociclib (LEE011); AK174906; 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo [2,3-d]pyrimidine-6-carboxylic acid dimethylamide; Ribociclib [USAN:INN]; LEE011A; Tube013

Indication

Breast cancer; ICD 11: 2C60-2C65; Status: Phase 3 [1]; Solid tumour/cancer; ICD 11: 2A00-2F9Z; Status: Phase 3 [2]

• Drug Type: Small molecular drug

List of Combinatorial Drugs (CBD) Containing This Drug

7 Investigative Drug Combination(s) Consisting of This drug

Normalized Drug Combination Synergy Score

Synergy scores were normalized using Min-Max Scaling to facilitate visual comparisons.

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
IT-141 + LEE011	DCVH9AU	IT-141	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
LEE011 + Everolimus	DCR0X34	Everolimus	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
LEE011 + Vorinostat	DCNZ7TA	Vorinostat	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Lenalidomide + LEE011	DCIJ6MU	Lenalidomide	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Pyrazinamide + LEE011	DCZSP0W	Pyrazinamide	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Teriflunomide + LEE011	DC8DCYG	Teriflunomide	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Venglustat + LEE011	DCFJMGM	Venglustat	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]

21 Clinical Trial Drug Combination(s) Consisting of This drug

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
Arry-162 + LEE011	DC993H4	Arry-162	Solid Tumors Harboring a BRAF V600 Mutation	[4]
Arry-162 + LEE011	DCPPDY6	Arry-162	Locally Advanced or Metastatic NRAS Mutant Melanoma	[5]
Belinostat + LEE011	DC8MSF1	Belinostat	Metastatic Breast Cancer	[6]
Ceritinib + LEE011	DC3QIP4	Ceritinib	Non-small Cell Lung Cancer	[7]
Dexamethasone + LEE011	DCUH85L	Dexamethasone	Acute Lymphoblastic Leukemia ALL	[8]
EGF816 + LEE011	DCJPVYX	EGF816	EGFR-mutant Non-small Cell Lung Cancer	[9]
Enzalutamide + LEE011	DCHW86C	Enzalutamide	Castration-Resistant Prostate Carcinoma	[10]
Everolimus + LEE011	DCS1DQL	Everolimus	Pediatric Cancer	[11]
Exemestane + LEE011	DC33SHL	Exemestane	Breast Cancer	[12]
Fulvestrant + LEE011	DCW30QW	Fulvestrant	Breast Cancer	[13]
Gemcitabine + LEE011	DC995TY	Gemcitabine	Anaplastic Astrocytoma	[14]
LEE011 + LGX818	DCDNY6S	LGX818	Locally Advanced Metastatic BRAF Mutant Melanoma	[15]
LEE011 + LEE011	DCEMS9W	LEE011	Triple Negative Breast Cancer	[16]
Letrozole + LEE011	DCS02AM	Letrozole	Breast Cancer	[17]
Ruxolitinib + LEE011	DC2E0H7	Ruxolitinib	Myelofibrosis	[18]
Temozolomide + LEE011	DCDQPZ4	Temozolomide	Neuroblastoma	[19]
Temozolomide + LEE011	DCY7510	Temozolomide	Pediatric Cancer	[11]
Trametinib + LEE011	DC6HSDF	Trametinib	Solid Tumors for Phase Ib	[20]
Tucatinib + LEE011	DC3GOV2	Tucatinib	Anatomic Stage II Breast Cancer AJCC v8	[21]
Everolimus + LEE011	DCCWEJZ	Everolimus	Neuroendocrine Tumors	[22]
Letrozole + LEE011	DC6QCIJ	Letrozole	Early Breast Cancer	[23]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7383).
• [3] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [4] ClinicalTrials.gov (NCT01543698) A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
• [5] ClinicalTrials.gov (NCT01781572) A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
• [6] ClinicalTrials.gov (NCT04315233) Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics
• [7] ClinicalTrials.gov (NCT02292550) Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.
• [8] ClinicalTrials.gov (NCT03740334) Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL
• [9] ClinicalTrials.gov (NCT03333343) Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
• [10] ClinicalTrials.gov (NCT02555189) Enzalutamide With Ribociclib in Treating Patients With Metastatic Castrate-Resistant, Chemotherapy Naive Prostate Cancer That Retains Retinoblastoma Expression
• [11] ClinicalTrials.gov (NCT02813135) European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors
• [12] ClinicalTrials.gov (NCT01857193) Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer
• [13] ClinicalTrials.gov (NCT02088684) Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
• [14] ClinicalTrials.gov (NCT03434262) SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors
• [15] ClinicalTrials.gov (NCT01777776) Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
• [16] ClinicalTrials.gov (NCT03090165) Ribociclib and Bicalutamide in AR+ TNBC
• [17] ClinicalTrials.gov (NCT01872260) Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
• [18] ClinicalTrials.gov (NCT02370706) Study of the Safety of PIM447 in Combination With Ruxolitinib (INC424) and LEE011 in Patients With Myelofibrosis
• [19] ClinicalTrials.gov (NCT05429502) 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
• [20] ClinicalTrials.gov (NCT02703571) Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
• [21] ClinicalTrials.gov (NCT05319873) Ribociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast Cancer
• [22] ClinicalTrials.gov (NCT03070301) A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors
• [23] ClinicalTrials.gov (NCT01919229) A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)