Details of the Drug Combinations

General Information of This Drug (ID: DMEXMYK)

• Drug Name: Alpelisib (DMEXMYK)
• Synonyms: alpelisib; 1217486-61-7; BYL-719; BYL719; UNII-08W5N2C97Q; BYL 719; Alpelisib (BYL719); (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide; NVP-BYL719; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide; CHEMBL2396661; 08W5N2C97Q; AK146107; C19H22F3N5O2S; (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)-pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide

Indication

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

• Drug Type: Small molecular drug

List of Combinatorial Drugs (CBD) Containing This Drug

5 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
Alpelisib + Panobinostat	DCNTPF2	Panobinostat	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Alpelisib + Acalabrutinib	DC358A7	Acalabrutinib	Diffuse large B cell lymphoma (Cell Line: TMD8)	[3]
Alpelisib + Marizomib	DCBHUGV	Marizomib	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[3]
Alpelisib + Ibrutinib	DC9T5MF	Ibrutinib	Diffuse large B cell lymphoma (Cell Line: TMD8)	[3]
Alpelisib + Ruxolitinib	DC2GFDW	Ruxolitinib	Hodgkin lymphoma (Cell Line: L-1236)	[4]

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

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
Alpelisib + Capecitabine	DCDPQPJ	Capecitabine	Metastatic Breast Cancer	[5]
Alpelisib + Letrozole	DCAOYYN	Letrozole	Breast Cancer	[6]
Alpelisib + Letrozole	DC3K9YO	Letrozole	Metastatic or Locally-advanced Unresectable Breast Cancer	[7]
Alpelisib + Capecitabine	DC52PIO	Capecitabine	Rectal Cancer	[8]
Alpelisib + BGJ398	DCBYJ7X	BGJ398	Advanced Solid Tumors	[9]
Alpelisib + Zarnestra	DCPOZQT	Zarnestra	HNSCC	[10]
Arry-162 + Alpelisib	DC4O3K4	Arry-162	Advanced and Selected Solid Tumors	[11]
Everolimus + Alpelisib	DC1800C	Everolimus	Neoplasms	[12]
Exemestane + Alpelisib	DCDZQPO	Exemestane	Neoplasms	[12]
Exemestane + Alpelisib	DCKL9HQ	Exemestane	Metastatic or Locally-advanced Unresectable Breast Cancer	[7]
Fulvestrant + Alpelisib	DC1WHOV	Fulvestrant	Breast Cancer	[13]
RAD-1901 + Alpelisib	DCBLD99	RAD-1901	Breast Cancer	[14]
Sotrastaurin acetate + Alpelisib	DC3OYDW	Sotrastaurin acetate	Uveal Melanoma	[15]
Trametinib + Alpelisib	DCDEX6L	Trametinib	Meningioma	[16]
Fulvestrant + Alpelisib	DCXNTQ2	Fulvestrant	Breast Cancer	[17]
Fulvestrant + Alpelisib	DCG8FJE	Fulvestrant	Breast Cancer	[18]
Fulvestrant + Alpelisib	DCCVL62	Fulvestrant	Breast Cancer	[19]
Olaparib + Alpelisib	DCH2166	Olaparib	Ovarian Cancer	[20]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [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: 7955).
• [3] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [4] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [5] ClinicalTrials.gov (NCT01300962) Study of BKM120 or BYL719 and Capecitabine in Patients With Metastatic Breast Cancer
• [6] ClinicalTrials.gov (NCT01872260) Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
• [7] ClinicalTrials.gov (NCT01870505) BYL719 Plus Letrozole or Exemestane for Patients With Hormone-Receptor Positive Locally-Advanced Unresectable or Metastatic Breast Cancer
• [8] ClinicalTrials.gov (NCT02550743) BrUOG 302:BYL719, Capecitabine and Radiation for Rectal Cancer: A Brown University Oncology Research Group Study
• [9] ClinicalTrials.gov (NCT01928459) Phase 1b Trial of BGJ398/BYL719 in Solid Tumors
• [10] ClinicalTrials.gov (NCT04997902) Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
• [11] ClinicalTrials.gov (NCT01449058) A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
• [12] ClinicalTrials.gov (NCT02077933) Study of Safety and Efficacy of Alpelisib With Everolimus or Alpelisib With Everolimus and Exemestane in Advanced Breast Cancer Patients, Renal Cell Cancer and Pancreatic Tumors
• [13] ClinicalTrials.gov (NCT02088684) Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
• [14] ClinicalTrials.gov (NCT05563220) Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer
• [15] ClinicalTrials.gov (NCT02273219) Trial of AEB071 in Combination With BYL719 in Patients With Melanoma
• [16] ClinicalTrials.gov (NCT03631953) Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas
• [17] ClinicalTrials.gov (NCT05090358) Preventing High Blood Sugar in People Being Treated for Metastatic Breast Cancer
• [18] ClinicalTrials.gov (NCT03056755) Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
• [19] ClinicalTrials.gov (NCT02437318) Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.
• [20] ClinicalTrials.gov (NCT04729387) Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected