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Entrectinib

January 01, 1970

Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors.[5] It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (TRK) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK).[5]

Entrectinib
Clinical data
Trade namesRozlytrek
Other namesRXDX-101, NMS-E628
AHFS/Drugs.comMonograph
MedlinePlusa619049
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classAntineoplastic agent
ATC code
Legal status
Legal status
Identifiers
  • N-[5-(3,5-Difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide
CAS Number
  • 1108743-60-7
PubChem CID
  • 25141092
PubChem SID
  • 347828307
DrugBank
  • DB11986
ChemSpider
  • 24808589
UNII
  • L5ORF0AN1I
KEGG
  • D10926
ChEBI
  • CHEBI:195558
ChEMBL
  • ChEMBL1983268
Chemical and physical data
FormulaC31H34F2N6O2
Molar mass560.650 g·mol−1
3D model (JSmol)
  • Interactive image
  • CN1CCN(c2ccc(C(=O)Nc3n[nH]c4ccc(Cc5cc(F)cc(F)c5)cc34)c(NC3CCOCC3)c2)CC1
  • InChI=1S/C31H34F2N6O2/c1-38-8-10-39(11-9-38)25-3-4-26(29(19-25)34-24-6-12-41-13-7-24)31(40)35-30-27-17-20(2-5-28(27)36-37-30)14-21-15-22(32)18-23(33)16-21/h2-5,15-19,24,34H,6-14H2,1H3,(H2,35,36,37,40)
  • Key:HAYYBYPASCDWEQ-UHFFFAOYSA-N

The most common side effects include tiredness, constipation, dysgeusia (taste disturbances), edema (swelling with fluid retention), dizziness, diarrhea, nausea (feeling sick), dysesthesia (unpleasant and abnormal feeling when touched), dyspnea (difficulty breathing), anemia (low red blood cell count), increased weight, increased blood creatinine (possible sign of kidney problems), pain, cognitive disorders (problems with ability to think, learn and remember), vomiting, cough, and fever.[6][8]

It was approved for medical use in the United States in August 2019,[8][9][10] in Australia in May 2020,[1] and in the European Union in July 2020.[6]

Medical uses edit

In the US, entrectinib is indicated to treat patients whose cancers are ROS1-positive (have a specific genetic feature (biomarker)).[5] It is to be used in those with solid tumors that:[11]

  • are caused by certain abnormal neurotrophic tyrosine receptor kinase (NTRK) genes, and
  • have spread or if surgery to remove their cancer is likely to cause severe complications, and
  • there is no acceptable treatment, or the cancer grew or spread on other treatment

Entrectinib is not approved for use in those less than twelve years of age.[5][6][11]

In the European Union, entrectinib as monotherapy is indicated for the treatment of adults and adolescents twelve years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion,[6]

  • who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and[6]
  • who have not received a prior NTRK inhibitor[6]
  • who have no satisfactory treatment options.[6]

It is also indicated for the treatment of adults with ROS1 positive, advanced non small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.[6]

Side effects edit

The common side effects of entrectinib include fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia and vision disorders.[8]

The most serious side effects of entrectinib are congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation and vision disorders.[8]

History edit

In the U.S., entrectinib has orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC).[12][failed verification] It has an EU orphan designation for neuroblastoma.[13] FDA approved entrectinib for people with ROS1-positive, metastatic non-small cell lung cancer and NTRK gene fusion-positive solid tumours.[14] It is first FDA-approved treatment designed to target both ROS1 and NTRK that also shows response in cancer that has spread to the brain.[15] In June 2019, the Japanese Ministry of Health, Labour and Welfare (MHLW) approved the agent for the treatment of adult and pediatric patients with NTRK fusion–positive, advanced recurrent solid tumors.[16]

The U.S. Food and Drug Administration (FDA) approved entrectinib based on the evidence from four clinical trials of 355 patients with various types of solid tumors: Trial 1 (EudraCT 2012-000148-88), Trial 2 (NCT02097810), Trial 3 (NCT02568267),[17] and Trial 4 (NCT02650401).[18] The trials were conducted in the United States, Europe and Asia/Pacific region.[18][11]

The FDA granted entrectinib accelerated approval, priority review, breakthrough therapy, and orphan drug designation.[8] The approval of Rozlytrek was granted to Genentech, Inc.[8]

Mechanism of action edit

The process of tumorigenesis frequently involves protein kinase activation events, which can result from either mutations, or chromosomal rearrangements.[19][20] Gene rearrangements, leading to the expression of constitutively activated fusion tyrosine kinase receptors, have been increasingly identified as a common feature of malignancies over the last three decades, and success has been demonstrated using these rearrangements as targets for drug development.[20][21]

The expression of such gene fusions in a tumor can create a phenomenon termed 'oncogene addiction' in which the tumor becomes dependent on signaling by the aberrant kinase pathway, thus rendering its survival and continued proliferation exquisitely sensitive to targeted inhibition with small molecule tyrosine kinase inhibitor drugs.[20] Expression of the proteins encoded by these tyrosine kinase fusion genes can, in most cases, be shown to function independently as oncogenic drivers, capable of activating critical downstream pathways involved in the malignant phenotype, resulting in transformation of cells in vitro.[20] Some of the most important kinases that have been shown to undergo rearrangement in human cancers include the anaplastic lymphoma kinase (ALK), ROS1 kinase, and the neurotrophic receptor tyrosine kinases (NTRKs).[20][21][22][23]

Entrectinib is a selective tyrosine kinase inhibitor with specificity, at low nanomolar concentrations, for all of three Trk proteins (encoded by the NTRK1, 2, and 3 genes, respectively) as well as the ROS1, and ALK receptor tyrosine kinases.[24] The drug is orally administered, once daily, and is being studied[when?] in patients whose tumors have been shown to have fusions in NTRK1/2/3, ALK, or ROS1.[25] As a ROS1 inhibitor, entrectinib has demonstrated in cellular anti-proliferative studies to have a 36-fold greater potency against ROS1 as compared with another commercially available ROS1 inhibitor, crizotinib.[26]

Target TrkA TrkB TrkC ROS1 ALK
IC50 (nM) 1.7 0.1 0.1 0.2 1.6[27]

Entrectinib has also demonstrated in-vitro efficacy against potential Trk inhibitor resistance mutations such as NTRK1 F589L, NTRK1 V573M, NTRK1 G667S.[26]

Clinical development edit

Entrectinib is currently[when?] being tested in a global phase II basket clinical trial called STARTRK-2.[17] Interim results from two ongoing phase 1 trials have been reported at the 2016 AACR American Association for Cancer Research Conference in April 2016:[26] among the patients treated with entrectinib, four patients had tumors harboring NTRK fusions, including patients with non-small cell lung cancer (NSCLC), mCRC, salivary gland cancer, and astrocytoma.[citation needed]

The preliminary results seen with entrectinib in the phase I studies of patients with NTRK/ROS1/ALK fusions have led to the initiation of an open-label, multicenter, global, phase II basket study[17] to examine the use of entrectinib in patients having tumors with these gene rearrangements. The study will enroll any patient with a solid tumor having evidence of an NTRK/ROS1/ALK fusion, assuming the patient meets all other entry criteria. Examples of such tumor types include NSCLC, mCRC, salivary gland cancer, sarcoma, melanoma, thyroid cancer, glioblastoma, astrocytoma, cholangiocarcinoma, lymphoma and others.[citation needed]

Society and culture edit

Legal status edit

It was approved for medical use in the United States in August 2019,[10] and in Australia in May 2020.[1]

Economics edit

Investigations of entrectinib were conducted by Ignyta Pharmaceuticals.[28] On 21 December 2017, Roche announced plans to buy Ignyta for $1.7 billion.[29]

Names edit

Entrectinib is the International nonproprietary name (INN).[30]

References edit

  1. ^ a b c d "Rozlytrek Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 25 May 2020. Retrieved 16 August 2020.
  2. ^ "Rozlytrek Product information". Health Canada. Retrieved 29 May 2022.
  3. ^ "Summary Basis of Decision (SBD) for Rozlytrek". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  4. ^ "Rozlytrek 100 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). Retrieved 11 September 2020.
  5. ^ a b c d e "Rozlytrek- entrectinib capsule". DailyMed. 8 June 2020. Retrieved 16 August 2020.
  6. ^ a b c d e f g h i "Rozlytrek EPAR". European Medicines Agency (EMA). 26 May 2020. Retrieved 11 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ^ "Rozlytrek Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  8. ^ a b c d e f "FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor". U.S. Food and Drug Administration (FDA) (Press release). 15 August 2019. from the original on 14 September 2019. Retrieved 23 November 2019.   This article incorporates text from this source, which is in the public domain.
  9. ^ "FDA Approves Genentech's Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors". Genentech (Press release). Retrieved 16 August 2019.
  10. ^ a b "Drug Approval Package: Rozlytrek". U.S. Food and Drug Administration (FDA). 16 September 2019. Retrieved 23 November 2019.
  11. ^ a b c "Drug Trials Snapshots: Rozlytrek (solid tumors)". U.S. Food and Drug Administration (FDA). 13 September 2019. Retrieved 23 November 2019.  This article incorporates text from this source, which is in the public domain.
  12. ^ . Archived from the original on 31 October 2018. Retrieved 20 April 2016.
  13. ^ House DW (8 December 2015). "Ignyta's entrectinib an Orphan Drug in Europe for neuroblastoma". Seeking Alpha.
  14. ^ "FDA approves Roche's Rozlytrek (Entrectinib) for people with ROS1-positive, metastatic non-small cell lung cancer and NTRK gene fusion-positive solid tumours". F. Hoffmann-La Roche Ltd.
  15. ^ . TargetedOnc. Archived from the original on 16 August 2019. Retrieved 16 August 2019.
  16. ^ "Japan becomes the first country to approve Roche's personalised medicine Rozlytrek". Roche (Press release). 18 June 2019. Retrieved 23 November 2019.
  17. ^ a b c Clinical trial number NCT02568267 for "Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) (STARTRK-2)" at ClinicalTrials.gov
  18. ^ a b "Drug Trials Snapshots: Rozlytrek (non-small cell lung cancer)". U.S. Food and Drug Administration (FDA). 12 September 2019. Retrieved 23 November 2019.  This article incorporates text from this source, which is in the public domain.
  19. ^ Puig de la Bellacasa R, Karachaliou N, Estrada-Tejedor R, Teixidó J, Costa C, Borrell JI (April 2013). "ALK and ROS1 as a joint target for the treatment of lung cancer: a review". Translational Lung Cancer Research. 2 (2): 72–86. doi:10.3978/j.issn.2218-6751.2013.03.1 (inactive 31 January 2024). PMC 4369855. PMID 25806218.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  20. ^ a b c d e Shaw AT, Hsu PP, Awad MM, Engelman JA (November 2013). "Tyrosine kinase gene rearrangements in epithelial malignancies". Nature Reviews. Cancer. 13 (11): 772–787. doi:10.1038/nrc3612. PMC 3902129. PMID 24132104.
  21. ^ a b Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C (September 2014). "The landscape of kinase fusions in cancer". Nature Communications. 5: 4846. Bibcode:2014NatCo...5.4846S. doi:10.1038/ncomms5846. PMC 4175590. PMID 25204415.
  22. ^ Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, et al. (20 January 2014). "Kinase fusions are frequent in Spitz tumours and spitzoid melanomas". Nature Communications. 5: 3116. Bibcode:2014NatCo...5.3116W. doi:10.1038/ncomms4116. PMC 4084638. PMID 24445538.
  23. ^ Berge EM, Doebele RC (February 2014). "Targeted therapies in non-small cell lung cancer: emerging oncogene targets following the success of epidermal growth factor receptor". Seminars in Oncology. 41 (1): 110–125. doi:10.1053/j.seminoncol.2013.12.006. PMC 4159759. PMID 24565585.
  24. ^ Iyer R, Wehrmann L, Golden RL, Naraparaju K, Croucher JL, MacFarland SP, et al. (March 2016). "Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model". Cancer Letters. 372 (2): 179–186. doi:10.1016/j.canlet.2016.01.018. PMC 4792275. PMID 26797418.
  25. ^ Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, et al. (April 2016). "Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications". Molecular Cancer Therapeutics. 15 (4): 628–639. doi:10.1158/1535-7163.MCT-15-0758. PMID 26939704.
  26. ^ a b c Drilon A, De Braud FG, Siena S, Ou SH, Patel M, Ahn MJ, et al. (July 2016). (PDF). Cancer Research. 15 (76 14_Supplement): CT007. doi:10.1158/1538-7445.AM2016-CT007. Archived from the original (PDF) on 16 August 2016.
  27. ^ Siena S, Drilon AE, Ou IS, Farago AF, Patel M, Bauer TM, Hong D, Liu SV, Lee J, Patel R, Schechet L (September 2015). "29LBA Entrectinib (RXDX-101), an oral pan-Trk, ROS1, and ALK inhibitor in patients with advanced solid tumors harboring gene rearrangements". European Journal of Cancer. 51: S724–5. doi:10.1016/S0959-8049(16)31947-5.
  28. ^ Pacenta HL, Macy ME (2018). "Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma". Drug Design, Development and Therapy. 12: 3549–3561. doi:10.2147/DDDT.S147384. PMC 6204873. PMID 30425456.
  29. ^ Mulier T, Naomi K (22 December 2017). "Roche to Buy U.S. Cancer-Drug Maker Ignyta for $1.7 Billion". Bloomberg. Retrieved 16 February 2018.
  30. ^ World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1): 114. hdl:10665/331046.

External links edit

  • "Entrectinib". Drug Information Portal. U.S. National Library of Medicine.
  • "Entrectinib". NCI Drug Dictionary. National Cancer Institute.
  • "Entrectinib". National Cancer Institute. 16 September 2019.

January 01, 1970
entrectinib, sold, under, brand, name, rozlytrek, anti, cancer, medication, used, treat, ros1, positive, small, cell, lung, cancer, ntrk, fusion, positive, solid, tumors, selective, tyrosine, kinase, inhibitor, tropomyosin, receptor, kinases, oncogene, ros1, a. Entrectinib sold under the brand name Rozlytrek is an anti cancer medication used to treat ROS1 positive non small cell lung cancer and NTRK fusion positive solid tumors 5 It is a selective tyrosine kinase inhibitor TKI of the tropomyosin receptor kinases TRK A B and C C ros oncogene 1 ROS1 and anaplastic lymphoma kinase ALK 5 EntrectinibClinical dataTrade namesRozlytrekOther namesRXDX 101 NMS E628AHFS Drugs comMonographMedlinePlusa619049License dataUS DailyMed Entrectinib US FDA RozlytrekPregnancycategoryAU D 1 Routes ofadministrationBy mouthDrug classAntineoplastic agentATC codeL01EX14 WHO Legal statusLegal statusAU S4 Prescription only 1 CA only 2 3 UK POM Prescription only 4 US only 5 EU Rx only 6 7 IdentifiersIUPAC name N 5 3 5 Difluorobenzyl 1H indazol 3 yl 4 4 methyl 1 piperazinyl 2 tetrahydro 2H pyran 4 ylamino benzamideCAS Number1108743 60 7PubChem CID25141092PubChem SID347828307DrugBankDB11986ChemSpider24808589UNIIL5ORF0AN1IKEGGD10926ChEBICHEBI 195558ChEMBLChEMBL1983268Chemical and physical dataFormulaC 31H 34F 2N 6O 2Molar mass560 650 g mol 13D model JSmol Interactive imageSMILES CN1CCN c2ccc C O Nc3n nH c4ccc Cc5cc F cc F c5 cc34 c NC3CCOCC3 c2 CC1InChI InChI 1S C31H34F2N6O2 c1 38 8 10 39 11 9 38 25 3 4 26 29 19 25 34 24 6 12 41 13 7 24 31 40 35 30 27 17 20 2 5 28 27 36 37 30 14 21 15 22 32 18 23 33 16 21 h2 5 15 19 24 34H 6 14H2 1H3 H2 35 36 37 40 Key HAYYBYPASCDWEQ UHFFFAOYSA N The most common side effects include tiredness constipation dysgeusia taste disturbances edema swelling with fluid retention dizziness diarrhea nausea feeling sick dysesthesia unpleasant and abnormal feeling when touched dyspnea difficulty breathing anemia low red blood cell count increased weight increased blood creatinine possible sign of kidney problems pain cognitive disorders problems with ability to think learn and remember vomiting cough and fever 6 8 It was approved for medical use in the United States in August 2019 8 9 10 in Australia in May 2020 1 and in the European Union in July 2020 6 Contents 1 Medical uses 2 Side effects 3 History 4 Mechanism of action 5 Clinical development 6 Society and culture 6 1 Legal status 6 2 Economics 6 3 Names 7 References 8 External linksMedical uses editIn the US entrectinib is indicated to treat patients whose cancers are ROS1 positive have a specific genetic feature biomarker 5 It is to be used in those with solid tumors that 11 are caused by certain abnormal neurotrophic tyrosine receptor kinase NTRK genes andhave spread or if surgery to remove their cancer is likely to cause severe complications andthere is no acceptable treatment or the cancer grew or spread on other treatment Entrectinib is not approved for use in those less than twelve years of age 5 6 11 In the European Union entrectinib as monotherapy is indicated for the treatment of adults and adolescents twelve years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase NTRK gene fusion 6 who have a disease that is locally advanced metastatic or where surgical resection is likely to result in severe morbidity and 6 who have not received a prior NTRK inhibitor 6 who have no satisfactory treatment options 6 It is also indicated for the treatment of adults with ROS1 positive advanced non small cell lung cancer NSCLC not previously treated with ROS1 inhibitors 6 Side effects editThe common side effects of entrectinib include fatigue constipation dysgeusia edema dizziness diarrhea nausea dysesthesia dyspnea myalgia cognitive impairment weight gain cough vomiting fever arthralgia and vision disorders 8 The most serious side effects of entrectinib are congestive heart failure central nervous system effects skeletal fractures hepatotoxicity hyperuricemia QT prolongation and vision disorders 8 History editIn the U S entrectinib has orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA TrkB TrkC ROS1 and ALK positive non small cell lung cancer NSCLC and metastatic colorectal cancer mCRC 12 failed verification It has an EU orphan designation for neuroblastoma 13 FDA approved entrectinib for people with ROS1 positive metastatic non small cell lung cancer and NTRK gene fusion positive solid tumours 14 It is first FDA approved treatment designed to target both ROS1 and NTRK that also shows response in cancer that has spread to the brain 15 In June 2019 the Japanese Ministry of Health Labour and Welfare MHLW approved the agent for the treatment of adult and pediatric patients with NTRK fusion positive advanced recurrent solid tumors 16 The U S Food and Drug Administration FDA approved entrectinib based on the evidence from four clinical trials of 355 patients with various types of solid tumors Trial 1 EudraCT 2012 000148 88 Trial 2 NCT02097810 Trial 3 NCT02568267 17 and Trial 4 NCT02650401 18 The trials were conducted in the United States Europe and Asia Pacific region 18 11 The FDA granted entrectinib accelerated approval priority review breakthrough therapy and orphan drug designation 8 The approval of Rozlytrek was granted to Genentech Inc 8 Mechanism of action editThe process of tumorigenesis frequently involves protein kinase activation events which can result from either mutations or chromosomal rearrangements 19 20 Gene rearrangements leading to the expression of constitutively activated fusion tyrosine kinase receptors have been increasingly identified as a common feature of malignancies over the last three decades and success has been demonstrated using these rearrangements as targets for drug development 20 21 The expression of such gene fusions in a tumor can create a phenomenon termed oncogene addiction in which the tumor becomes dependent on signaling by the aberrant kinase pathway thus rendering its survival and continued proliferation exquisitely sensitive to targeted inhibition with small molecule tyrosine kinase inhibitor drugs 20 Expression of the proteins encoded by these tyrosine kinase fusion genes can in most cases be shown to function independently as oncogenic drivers capable of activating critical downstream pathways involved in the malignant phenotype resulting in transformation of cells in vitro 20 Some of the most important kinases that have been shown to undergo rearrangement in human cancers include the anaplastic lymphoma kinase ALK ROS1 kinase and the neurotrophic receptor tyrosine kinases NTRKs 20 21 22 23 Entrectinib is a selective tyrosine kinase inhibitor with specificity at low nanomolar concentrations for all of three Trk proteins encoded by the NTRK1 2 and 3 genes respectively as well as the ROS1 and ALK receptor tyrosine kinases 24 The drug is orally administered once daily and is being studied when in patients whose tumors have been shown to have fusions in NTRK1 2 3 ALK or ROS1 25 As a ROS1 inhibitor entrectinib has demonstrated in cellular anti proliferative studies to have a 36 fold greater potency against ROS1 as compared with another commercially available ROS1 inhibitor crizotinib 26 Target TrkA TrkB TrkC ROS1 ALK IC50 nM 1 7 0 1 0 1 0 2 1 6 27 Entrectinib has also demonstrated in vitro efficacy against potential Trk inhibitor resistance mutations such as NTRK1 F589L NTRK1 V573M NTRK1 G667S 26 Clinical development editEntrectinib is currently when being tested in a global phase II basket clinical trial called STARTRK 2 17 Interim results from two ongoing phase 1 trials have been reported at the 2016 AACR American Association for Cancer Research Conference in April 2016 26 among the patients treated with entrectinib four patients had tumors harboring NTRK fusions including patients with non small cell lung cancer NSCLC mCRC salivary gland cancer and astrocytoma citation needed The preliminary results seen with entrectinib in the phase I studies of patients with NTRK ROS1 ALK fusions have led to the initiation of an open label multicenter global phase II basket study 17 to examine the use of entrectinib in patients having tumors with these gene rearrangements The study will enroll any patient with a solid tumor having evidence of an NTRK ROS1 ALK fusion assuming the patient meets all other entry criteria Examples of such tumor types include NSCLC mCRC salivary gland cancer sarcoma melanoma thyroid cancer glioblastoma astrocytoma cholangiocarcinoma lymphoma and others citation needed Society and culture editLegal status edit It was approved for medical use in the United States in August 2019 10 and in Australia in May 2020 1 Economics edit Investigations of entrectinib were conducted by Ignyta Pharmaceuticals 28 On 21 December 2017 Roche announced plans to buy Ignyta for 1 7 billion 29 Names edit Entrectinib is the International nonproprietary name INN 30 References edit a b c d Rozlytrek Australian prescription medicine decision summary Therapeutic Goods Administration TGA 25 May 2020 Retrieved 16 August 2020 Rozlytrek Product information Health Canada Retrieved 29 May 2022 Summary Basis of Decision SBD for Rozlytrek Health Canada 23 October 2014 Retrieved 29 May 2022 Rozlytrek 100 mg hard capsules Summary of Product Characteristics SmPC emc Retrieved 11 September 2020 a b c d e Rozlytrek entrectinib capsule DailyMed 8 June 2020 Retrieved 16 August 2020 a b c d e f g h i Rozlytrek EPAR European Medicines Agency EMA 26 May 2020 Retrieved 11 September 2020 Text was copied from this source which is c European Medicines Agency Reproduction is authorized provided the source is acknowledged Rozlytrek Product information Union Register of medicinal products Retrieved 3 March 2023 a b c d e f FDA approves third oncology drug that targets a key genetic driver of cancer rather than a specific type of tumor U S Food and Drug Administration FDA Press release 15 August 2019 Archived from the original on 14 September 2019 Retrieved 23 November 2019 nbsp This article incorporates text from this source which is in the public domain FDA Approves Genentech s Rozlytrek entrectinib for People With ROS1 Positive Metastatic Non Small Cell Lung Cancer and NTRK Gene Fusion Positive Solid Tumors Genentech Press release Retrieved 16 August 2019 a b Drug Approval Package Rozlytrek U S Food and Drug Administration FDA 16 September 2019 Retrieved 23 November 2019 a b c Drug Trials Snapshots Rozlytrek solid tumors U S Food and Drug Administration FDA 13 September 2019 Retrieved 23 November 2019 nbsp This article incorporates text from this source which is in the public domain Ignyta Receives Orphan Drug Designation From FDA For Entrectinib For The Treatment Of Molecularly Defined Subsets Of Non Small Cell Lung Cancer Archived from the original on 31 October 2018 Retrieved 20 April 2016 House DW 8 December 2015 Ignyta s entrectinib an Orphan Drug in Europe for neuroblastoma Seeking Alpha FDA approves Roche s Rozlytrek Entrectinib for people with ROS1 positive metastatic non small cell lung cancer and NTRK gene fusion positive solid tumours F Hoffmann La Roche Ltd FDA Approves Entrectinib for ROS1 NSCLC and NTRK Solid Tumors TargetedOnc Archived from the original on 16 August 2019 Retrieved 16 August 2019 Japan becomes the first country to approve Roche s personalised medicine Rozlytrek Roche Press release 18 June 2019 Retrieved 23 November 2019 a b c Clinical trial number NCT02568267 for Basket Study of Entrectinib RXDX 101 for the Treatment of Patients With Solid Tumors Harboring NTRK 1 2 3 Trk A B C ROS1 or ALK Gene Rearrangements Fusions STARTRK 2 at ClinicalTrials gov a b Drug Trials Snapshots Rozlytrek non small cell lung cancer U S Food and Drug Administration FDA 12 September 2019 Retrieved 23 November 2019 nbsp This article incorporates text from this source which is in the public domain Puig de la Bellacasa R Karachaliou N Estrada Tejedor R Teixido J Costa C Borrell JI April 2013 ALK and ROS1 as a joint target for the treatment of lung cancer a review Translational Lung Cancer Research 2 2 72 86 doi 10 3978 j issn 2218 6751 2013 03 1 inactive 31 January 2024 PMC 4369855 PMID 25806218 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of January 2024 link a b c d e Shaw AT Hsu PP Awad MM Engelman JA November 2013 Tyrosine kinase gene rearrangements in epithelial malignancies Nature Reviews Cancer 13 11 772 787 doi 10 1038 nrc3612 PMC 3902129 PMID 24132104 a b Stransky N Cerami E Schalm S Kim JL Lengauer C September 2014 The landscape of kinase fusions in cancer Nature Communications 5 4846 Bibcode 2014NatCo 5 4846S doi 10 1038 ncomms5846 PMC 4175590 PMID 25204415 Wiesner T He J Yelensky R Esteve Puig R Botton T Yeh I et al 20 January 2014 Kinase fusions are frequent in Spitz tumours and spitzoid melanomas Nature Communications 5 3116 Bibcode 2014NatCo 5 3116W doi 10 1038 ncomms4116 PMC 4084638 PMID 24445538 Berge EM Doebele RC February 2014 Targeted therapies in non small cell lung cancer emerging oncogene targets following the success of epidermal growth factor receptor Seminars in Oncology 41 1 110 125 doi 10 1053 j seminoncol 2013 12 006 PMC 4159759 PMID 24565585 Iyer R Wehrmann L Golden RL Naraparaju K Croucher JL MacFarland SP et al March 2016 Entrectinib is a potent inhibitor of Trk driven neuroblastomas in a xenograft mouse model Cancer Letters 372 2 179 186 doi 10 1016 j canlet 2016 01 018 PMC 4792275 PMID 26797418 Ardini E Menichincheri M Banfi P Bosotti R De Ponti C Pulci R et al April 2016 Entrectinib a Pan TRK ROS1 and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications Molecular Cancer Therapeutics 15 4 628 639 doi 10 1158 1535 7163 MCT 15 0758 PMID 26939704 a b c Drilon A De Braud FG Siena S Ou SH Patel M Ahn MJ et al July 2016 Abstract CT007 Entrectinib an oral pan Trk ROS1 and ALK inhibitor in TKI naive patients with advanced solid tumors harboring gene rearrangements Updated phase I results PDF Cancer Research 15 76 14 Supplement CT007 doi 10 1158 1538 7445 AM2016 CT007 Archived from the original PDF on 16 August 2016 Siena S Drilon AE Ou IS Farago AF Patel M Bauer TM Hong D Liu SV Lee J Patel R Schechet L September 2015 29LBA Entrectinib RXDX 101 an oral pan Trk ROS1 and ALK inhibitor in patients with advanced solid tumors harboring gene rearrangements European Journal of Cancer 51 S724 5 doi 10 1016 S0959 8049 16 31947 5 Pacenta HL Macy ME 2018 Entrectinib and other ALK TRK inhibitors for the treatment of neuroblastoma Drug Design Development and Therapy 12 3549 3561 doi 10 2147 DDDT S147384 PMC 6204873 PMID 30425456 Mulier T Naomi K 22 December 2017 Roche to Buy U S Cancer Drug Maker Ignyta for 1 7 Billion Bloomberg Retrieved 16 February 2018 World Health Organization 2016 International nonproprietary names for pharmaceutical substances INN recommended INN list 75 WHO Drug Information 30 1 114 hdl 10665 331046 External links edit Entrectinib Drug Information Portal U S National Library of Medicine Entrectinib NCI Drug Dictionary National Cancer Institute Entrectinib National Cancer Institute 16 September 2019 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Entrectinib amp oldid 1201882413, wikipedia, wiki, book, books, library,

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