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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Entrectinib: A New Selective Tyrosine Kinase Inhibitor Approved for the Treatment of Pediatric and Adult Patients with NTRK Fusionpositive, Recurrent or Advanced Solid Tumors

Author(s): Hind M. Osman and Meral Tuncbilek*

Volume 29, Issue 15, 2022

Published on: 01 April, 2022

Page: [2602 - 2616] Pages: 15

DOI: 10.2174/0929867328666210914121324

Price: $65

Abstract

Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. It was developed by Roche and initially approved in Japan in 2019 to treat pediatric and adult patients with NTRK fusionpositive, recurrent, or advanced solid tumors. In August 2019, entrectinib received accelerated approval by the U.S FDA for this indication. It is also the first FDA-approved drug designed to target both NTRK and ROS1.

Objective: We aim to summarize recent studies related to the synthesis, mechanism of action, and clinical trials of the newly approved selective tyrosine kinase inhibitor entrectinib.

Methods: We conduct a literature review of the research studies on the new highly-potent small-molecule entrectinib.

Conclusion: Entrectinib, based on three clinical studies (ALKA, STARTRK-1, and STARTRK-2), was well tolerated, with a manageable safety profile. It induced clinically meaningful responses in recurrent or advanced solid tumors associated with NTRK fusion- positive or ROS1+ NSCLC. It demonstrated substantial efficacy in patients with CNS metastases.

Keywords: Entrectinib, indazol benzamide, Trk ABC, ALK, ROS1 inhibitor, NTRK fusion-positive tumors.

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[1]
Lemmon, M.A.; Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell, 2010, 141(7), 1117-1134.
[http://dx.doi.org/10.1016/j.cell.2010.06.011] [PMID: 20602996]
[2]
McDonell, L.M.; Kernohan, K.D.; Boycott, K.M.; Sawyer, S.L. Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin. Hum. Mol. Genet., 2015, 24(R1), R60-R66.
[http://dx.doi.org/10.1093/hmg/ddv254] [PMID: 26152202]
[3]
Forbes, S.A.; Tang, G.; Bindal, N.; Bamford, S.; Dawson, E.; Cole, C.; Kok, C.Y.; Jia, M.; Ewing, R.; Menzies, A.; Teague, J.W.; Stratton, M.R.; Futreal, P.A. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res., 2010, 38(Database issue), D652-D657.
[http://dx.doi.org/10.1093/nar/gkp995] [PMID: 19906727]
[4]
Liu, D.; Offin, M.; Harnicar, S.; Li, B.T.; Drilon, A. Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther. Clin. Risk Manag., 2018, 14, 1247-1252.
[http://dx.doi.org/10.2147/TCRM.S147381] [PMID: 30050303]
[5]
Gatalica, Z.; Xiu, J.; Swensen, J.; Vranic, S. Molecular characterization of cancers with NTRK gene fusions. Mod. Pathol., 2019, 32(1), 147-153.
[http://dx.doi.org/10.1038/s41379-018-0118-3] [PMID: 30171197]
[6]
Cocco, E.; Scaltriti, M.; Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat. Rev. Clin. Oncol., 2018, 15(12), 731-747.
[http://dx.doi.org/10.1038/s41571-018-0113-0] [PMID: 30333516]
[7]
Shaw, A.T.; Gandhi, L.; Gadgeel, S.; Riely, G.J.; Cetnar, J.; West, H.; Camidge, D.R.; Socinski, M.A.; Chiappori, A.; Mekhail, T.; Chao, B.H.; Borghaei, H.; Gold, K.A.; Zeaiter, A.; Bordogna, W.; Balas, B.; Puig, O.; Henschel, V.; Ou, S.I. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol., 2016, 17(2), 234-242.
[http://dx.doi.org/10.1016/S1470-2045(15)00488-X] [PMID: 26708155]
[8]
Aisner, D.L.; Nguyen, T.T.; Paskulin, D.D.; Le, A.T.; Haney, J.; Schulte, N.; Chionh, F.; Hardingham, J.; Mariadason, J.; Tebbutt, N.; Doebele, R.C.; Weickhardt, A.J.; Varella-Garcia, M. ROS1 and ALK fusions in colorectal cancer, with evidence of intratumoral heterogeneity for molecular drivers. Mol. Cancer Res., 2014, 12(1), 111-118.
[http://dx.doi.org/10.1158/1541-7786.MCR-13-0479-T] [PMID: 24296758]
[9]
Uguen, A.; De Braekeleer, M. ROS1 fusions in cancer: a review. Future Oncol., 2016, 12(16), 1911-1928.
[http://dx.doi.org/10.2217/fon-2016-0050] [PMID: 27256160]
[10]
Vaishnavi, A.; Le, A.T.; Doebele, R.C. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov., 2015, 5(1), 25-34.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0765] [PMID: 25527197]
[11]
Jiang, T.; Wang, G.; Liu, Y.; Feng, L.; Wang, M.; Liu, J.; Chen, Y.; Ouyang, L. Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers. Acta Pharm. Sin. B, 2021, 11(2), 355-372.
[http://dx.doi.org/10.1016/j.apsb.2020.05.004] [PMID: 33643817]
[12]
Ducray, S.P.; Natarajan, K.; Garland, G.D.; Turner, S.D.; Egger, G. The transcriptional roles of ALK fusion proteins in tumorigenesis. Cancers (Basel), 2019, 11(8), 1-23.
[http://dx.doi.org/10.3390/cancers11081074] [PMID: 31366041]
[13]
Hallberg, B.; Palmer, R.H. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer, 2013, 13(10), 685-700.
[http://dx.doi.org/10.1038/nrc3580] [PMID: 24060861]
[14]
Drilon, A.; Jenkins, C.; Iyer, S.; Schoenfeld, A.; Keddy, C.; Davare, M.A. ROS1-dependent cancers - biology, diagnostics and therapeutics. Nat. Rev. Clin. Oncol., 2021, 18(1), 35-55.
[15]
Davare, M.A.; Saborowski, A.; Eide, C.A.; Tognon, C.; Smith, R.L.; Elferich, J.; Agarwal, A.; Tyner, J.W.; Shinde, U.P.; Lowe, S.W.; Druker, B.J. Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins. Proc. Natl. Acad. Sci. USA, 2013, 110(48), 19519-19524.
[http://dx.doi.org/10.1073/pnas.1319583110] [PMID: 24218589]
[16]
Rosell, R.; Carcereny, E.; Gervais, R.; Vergnenegre, A.; Massuti, B.; Felip, E.; Palmero, R.; Garcia-Gomez, R.; Pallares, C.; Sanchez, J.M.; Porta, R.; Cobo, M.; Garrido, P.; Longo, F.; Moran, T.; Insa, A.; De Marinis, F.; Corre, R.; Bover, I.; Illiano, A.; Dansin, E.; de Castro, J.; Milella, M.; Reguart, N.; Altavilla, G.; Jimenez, U.; Provencio, M.; Moreno, M.A.; Terrasa, J.; Muñoz-Langa, J.; Valdivia, J.; Isla, D.; Domine, M.; Molinier, O.; Mazieres, J.; Baize, N.; Garcia-Campelo, R.; Robinet, G.; Rodriguez-Abreu, D.; Lopez-Vivanco, G.; Gebbia, V.; Ferrera-Delgado, L.; Bombaron, P.; Bernabe, R.; Bearz, A.; Artal, A.; Cortesi, E.; Rolfo, C.; Sanchez-Ronco, M.; Drozdowskyj, A.; Queralt, C.; de Aguirre, I.; Ramirez, J.L.; Sanchez, J.J.; Molina, M.A.; Taron, M.; Paz-Ares, L. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol., 2012, 13(3), 239-246.
[http://dx.doi.org/10.1016/S1470-2045(11)70393-X] [PMID: 22285168]
[17]
Sequist, L.V.; Yang, J.C.H.; Yamamoto, N.; O’Byrne, K.; Hirsh, V.; Mok, T.; Geater, S.L.; Orlov, S.; Tsai, C.M.; Boyer, M.; Su, W.C.; Bennouna, J.; Kato, T.; Gorbunova, V.; Lee, K.H.; Shah, R.; Massey, D.; Zazulina, V.; Shahidi, M.; Schuler, M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol., 2013, 31(27), 3327-3334.
[http://dx.doi.org/10.1200/JCO.2012.44.2806] [PMID: 23816960]
[18]
Yan, W.; Lakkaniga, N.R.; Carlomagno, F.; Santoro, M.; McDonald, N.Q.; Lv, F.; Gunaganti, N.; Frett, B.; Li, H.Y. Insights into current tropomyosin receptor kinase (TRK) inhibitors: Development and clinical application. J. Med. Chem., 2019, 62(4), 1731-1760.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01092] [PMID: 30188734]
[19]
Cui, S.; Wang, Y.; Wang, Y.; Tang, X.; Ren, X.; Zhang, L.; Xu, Y.; Zhang, Z.; Zhang, Z.M.; Lu, X.; Ding, K. Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors. Eur. J. Med. Chem., 2019, 179, 470-482.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.064] [PMID: 31271959]
[20]
Smith, B.D.; Kaufman, M.D.; Leary, C.B.; Turner, B.A.; Wise, S.C.; Ahn, Y.M.; Booth, R.J.; Caldwell, T.M.; Ensinger, C.L.; Hood, M.M.; Lu, W.P.; Patt, T.W.; Patt, W.C.; Rutkoski, T.J.; Samarakoon, T.; Telikepalli, H.; Vogeti, L.; Vogeti, S.; Yates, K.M.; Chun, L.; Stewart, L.J.; Clare, M.; Flynn, D.L. Altiratinib inhibits tumor growth, invasion, angiogenesis, and microenvironment-mediated drug resistance via balanced inhibition of MET, TIE2, and VEGFR2. Mol. Cancer Ther., 2015, 14(9), 2023-2034.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-1105] [PMID: 26285778]
[21]
Patwardhan, P.P.; Ivy, K.S.; Musi, E.; de Stanchina, E.; Schwartz, G.K. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 2016, 7(4), 4093-4109.
[http://dx.doi.org/10.18632/oncotarget.6547] [PMID: 26675259]
[22]
Yakes, F.M.; Chen, J.; Tan, J.; Yamaguchi, K.; Shi, Y.; Yu, P.; Qian, F.; Chu, F.; Bentzien, F.; Cancilla, B.; Orf, J.; You, A.; Laird, A.D.; Engst, S.; Lee, L.; Lesch, J.; Chou, Y.C.; Joly, A.H. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol. Cancer Ther., 2011, 10(12), 2298-2308.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0264] [PMID: 21926191]
[23]
Bernard-Gauthier, V.; Mossine, A.V.; Mahringer, A.; Aliaga, A.; Bailey, J.J.; Shao, X.; Stauff, J.; Arteaga, J.; Sherman, P.; Grand’Maison, M.; Rochon, P.L.; Wängler, B.; Wängler, C.; Bartenstein, P.; Kostikov, A.; Kaplan, D.R.; Fricker, G.; Rosa-Neto, P.; Scott, P.J.H.; Schirrmacher, R. Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging. J. Med. Chem., 2018, 61(4), 1737-1743.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01607] [PMID: 29257860]
[24]
Bernard-Gauthier, V.; Bailey, J.J.; Mossine, A.V.; Lindner, S.; Vomacka, L.; Aliaga, A.; Shao, X.; Quesada, C.A.; Sherman, P.; Mahringer, A.; Kostikov, A.; Grand’Maison, M.; Rosa-Neto, P.; Soucy, J.P.; Thiel, A.; Kaplan, D.R.; Fricker, G.; Wängler, B.; Bartenstein, P.; Schirrmacher, R.; Scott, P.J.H. A kinome-wide selective radiolabeled TrkB/C inhibitor for in vitro and in vivo neuroimaging: Synthesis, preclinical evaluation, and first-in-human. J. Med. Chem., 2017, 60(16), 6897-6910.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00396] [PMID: 28696690]
[25]
Drilon, A.; Laetsch, T.W.; Kummar, S.; DuBois, S.G.; Lassen, U.N.; Demetri, G.D.; Nathenson, M.; Doebele, R.C.; Farago, A.F.; Pappo, A.S.; Turpin, B.; Dowlati, A.; Brose, M.S.; Mascarenhas, L.; Federman, N.; Berlin, J.; El-Deiry, W.S.; Baik, C.; Deeken, J.; Boni, V.; Nagasubramanian, R.; Taylor, M.; Rudzinski, E.R.; Meric-Bernstam, F.; Sohal, D.P.S.; Ma, P.C.; Raez, L.E.; Hechtman, J.F.; Benayed, R.; Ladanyi, M.; Tuch, B.B.; Ebata, K.; Cruickshank, S.; Ku, N.C.; Cox, M.C.; Hawkins, D.S.; Hong, D.S.; Hyman, D.M. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N. Engl. J. Med., 2018, 378(8), 731-739.
[http://dx.doi.org/10.1056/NEJMoa1714448] [PMID: 29466156]
[26]
Zage, P.E.; Graham, T.C.; Zeng, L.; Fang, W.; Pien, C.; Thress, K.; Omer, C.; Brown, J.L.; Zweidler-McKay, P.A. The selective Trk inhibitor AZ623 inhibits brain-derived neurotrophic factor-mediated neuroblastoma cell proliferation and signaling and is synergistic with topotecan. Cancer, 2011, 117(6), 1321-1391.
[http://dx.doi.org/10.1002/cncr.25674] [PMID: 20960503]
[27]
Shaw, A.T.; Yasothan, U.; Kirkpatrick, P. Crizotinib. Nat. Rev. Drug Discov., 2011, 10(12), 897-898.
[http://dx.doi.org/10.1038/nrd3600] [PMID: 22129984]
[28]
Dhillon, S.; Clark, M. Ceritinib: first global approval. Drugs, 2014, 74(11), 1285-1291.
[http://dx.doi.org/10.1007/s40265-014-0251-3] [PMID: 24980964]
[29]
Hida, T.; Nokihara, H.; Kondo, M.; Kim, Y.H.; Azuma, K.; Seto, T.; Takiguchi, Y.; Nishio, M.; Yoshioka, H.; Imamura, F.; Hotta, K.; Watanabe, S.; Goto, K.; Satouchi, M.; Kozuki, T.; Shukuya, T.; Nakagawa, K.; Mitsudomi, T.; Yamamoto, N.; Asakawa, T.; Asabe, R.; Tanaka, T.; Tamura, T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet, 2017, 390(10089), 29-39.
[http://dx.doi.org/10.1016/S0140-6736(17)30565-2] [PMID: 28501140]
[30]
Markham, A. Brigatinib: First Global Approval. Drugs, 2017, 77(10), 1131-1135.
[http://dx.doi.org/10.1007/s40265-017-0776-3] [PMID: 28597393]
[31]
Syed, Y.Y. Lorlatinib: First Global Approval. Drugs, 2019, 79(1), 93-98.
[http://dx.doi.org/10.1007/s40265-018-1041-0] [PMID: 30604291]
[32]
Han, S.Y. Trk inhibitors: Tissue-agnostic anti-cancer drugs. Pharmaceuticals (Basel), 2021, 14(7), 632.
[http://dx.doi.org/10.3390/ph14070632] [PMID: 34209967]
[33]
Roche. Japan becomes the first country to approve Roche’s personalised medicine Rozlytrek. 2019. Available from: https://www.roche.com/media/relea ses/med-cor-2019-06-18.htm
[34]
Lee, J.; Park, S.; Jung, H.A.; Sun, J.M.; Lee, S.H.; Ahn, J.S.; Park, K.; Ahn, M.J. Evaluating entrectinib as a treatment option for non-small cell lung cancer. Expert Opin. Pharmacother., 2020, 21(16), 1935-1942.
[http://dx.doi.org/10.1080/14656566.2020.1798932] [PMID: 32736487]
[35]
FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. 2019. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc
[36]
Scott, L.J. Larotrectinib: First Global Approval. Drugs, 2019, 79(2), 201-206.
[http://dx.doi.org/10.1007/s40265-018-1044-x] [PMID: 30635837]
[37]
Marcus, L.; Donoghue, M.; Aungst, S.; Myers, C.E.; Helms, W.S.; Shen, G.; Zhao, H.; Stephens, O.; Keegan, P.; Pazdur, R. FDA approval summary: entrectinib for the treatment of NTRK gene fusion solid tumors. Clin. Cancer Res., 2021, 27(4), 928-932.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-2771] [PMID: 32967940]
[38]
Ardini, E.; Siena, S. Entrectinib approval by EMA reinforces options for ROS1 and tumour agnostic NTRK targeted cancer therapies., 2020.
[http://dx.doi.org/10.1136/esmoopen-2020-000867]
[39]
Al-Salama, Z.T.; Keam, S.J. Entrectinib: First Global Approval. Drugs, 2019, 79(13), 1477-1483.
[http://dx.doi.org/10.1007/s40265-019-01177-y] [PMID: 31372957]
[40]
Delgado, J.; Pean, E.; Melchiorri, D.; Migali, C.; Josephson, F.; Enzmann, H.; Pignatti, F. The European Medicines Agency review of entrectinib for the treatment of adult or paediatric patients with solid tumours who have a neurotrophic tyrosine receptor kinase gene fusions and adult patients with non-small-cell lung cancer harbouring ROS1 rearrangements. ESMO Open, 2021, 6(2)100087
[http://dx.doi.org/10.1016/j.esmoop.2021.100087] [PMID: 33735800]
[41]
Menichincheri, M.; Ardini, E.; Magnaghi, P.; Avanzi, N.; Banfi, P.; Bossi, R.; Buffa, L.; Canevari, G.; Ceriani, L.; Colombo, M.; Corti, L.; Donati, D.; Fasolini, M.; Felder, E.; Fiorelli, C.; Fiorentini, F.; Galvani, A.; Isacchi, A.; Borgia, A.L.; Marchionni, C.; Nesi, M.; Orrenius, C.; Panzeri, A.; Pesenti, E.; Rusconi, L.; Saccardo, M.B.; Vanotti, E.; Perrone, E.; Orsini, P. Discovery of entrectinib: A new 3-aminoindazole as a potent anaplastic lymphoma kinase (ALK), c-ros oncogene 1 kinase (ROS1), and pan-tropomyosin receptor kinases (Pan-TRKs) inhibitor. J. Med. Chem., 2016, 59(7), 3392-3408.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00064] [PMID: 27003761]
[42]
Antonysamy, S.; Hirst, G.; Park, F.; Sprengeler, P.; Stappenbeck, F.; Steensma, R.; Wilson, M.; Wong, M. Fragment-based discovery of JAK-2 inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(1), 279-282.
[http://dx.doi.org/10.1016/j.bmcl.2008.08.064] [PMID: 19019674]
[43]
Orsini, P.; Menichincheri, M.; Vanotti, E.; Panzeri, A. Highly efficient synthesis of 5-benzyl-3-aminoindazoles. Tetrahedron Lett., 2009, 50(25), 3098-3100.
[http://dx.doi.org/10.1016/j.tetlet.2009.04.024]
[44]
Kuwano, R.; Yokogi, M. Suzuki-Miyaura cross-coupling of benzylic carbonates with arylboronic acids. Org. Lett., 2005, 7(5), 945-947.
[http://dx.doi.org/10.1021/ol050078q] [PMID: 15727481]
[45]
McLaughlin, M. Suzuki-Miyaura cross-coupling of benzylic phosphates with arylboronic acids. Org. Lett., 2005, 7(22), 4875-4878.
[http://dx.doi.org/10.1021/ol0517271] [PMID: 16235911]
[46]
Kuwano, R. Catalytic transformations of benzylic carboxylates and carbonates. Synthesis (Stuttg), 2009, 2009(7), 1049-1061.
[http://dx.doi.org/10.1055/s-0028-1088001]
[47]
Ardini, E.; Menichincheri, M.; Banfi, P.; Saccardo, M.B.; Rusconi, L.; Avanzi, N. In vitro and in vivo activity of NMS-E628 against ALK mutations resistant to Xalkori. Mol. Cancer Ther., 2011, 10(11), 10 [Suppl.].
[48]
De Braud, F.G.; Pilla, L.; Niger, M.; Damian, S.; Bardazza, B.; Martinetti, A. Phase 1 open label, dose escalation study of RXDX101, an oral pan-trk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations. J. Clin. Oncol., 2014, 32(15), 2502-2502.
[http://dx.doi.org/10.1200/jco.2014.32.15_suppl.2502]
[49]
Doebele, R.; Ahn, M.; Siena, S.; Drilon, A.; Krebs, M.; Lin, C. OA02.01 OA02.01 efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC). J. Thorac. Oncol., 2018, 13(10), S321-S322.
[http://dx.doi.org/10.1016/j.jtho.2018.08.239]
[50]
John, T.; Chiu, C.H.; Cho, B.C.; Fakih, M.; Farago, A.F.; Demetri, G.D. 364O Intracranial efficacy of entrectinib in patients with NTRK fusion-positive solid tumours and baseline CNS metastases. Ann. Oncol., 2020, 31, S397-S398.
[http://dx.doi.org/10.1016/j.annonc.2020.08.473]
[51]
Aveic, S.; Pantile, M.; Seydel, A.; Esposito, M.R.; Zanon, C.; Li, G.; Tonini, G.P. Combating autophagy is a strategy to increase cytotoxic effects of novel ALK inhibitor entrectinib in neuroblastoma cells. Oncotarget, 2016, 7(5), 5646-5663.
[http://dx.doi.org/10.18632/oncotarget.6778] [PMID: 26735175]
[52]
Ardini, E.; Menichincheri, M.; Banfi, P.; Bosotti, R.; De Ponti, C.; Pulci, R.; Ballinari, D.; Ciomei, M.; Texido, G.; Degrassi, A.; Avanzi, N.; Amboldi, N.; Saccardo, M.B.; Casero, D.; Orsini, P.; Bandiera, T.; Mologni, L.; Anderson, D.; Wei, G.; Harris, J.; Vernier, J.M.; Li, G.; Felder, E.; Donati, D.; Isacchi, A.; Pesenti, E.; Magnaghi, P.; Galvani, A. Entrectinib, a Pan-TRK, ROS1, and ALK inhibitor with activity in multiple molecularly defined cancer indications. Mol. Cancer Ther., 2016, 15(4), 628-639.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0758] [PMID: 26939704]
[53]
Ardini, E.; Menichincheri, M.; Banfi, P.; Casero, D.; Giorgini, M. L.; Saccardo, M. B. The ALK inhibitor NMS-E628 also potently inhibits ROS1 and induces tumor regression in ROS-driven models., 2013, 73(8), 2092-2092.
[54]
Anderson, D.; Ciomei, M.; Banfi, P.; Cribioli, S.; Ardini, E.; Galvani, A. Inhibition of Trk-driven tumors by the pan-Trk inhibitor RXDX-101. Eur. J. Cancer, 2014, 50, 101.
[http://dx.doi.org/10.1016/S0959-8049(14)70436-8]
[55]
Iyer, R.; Wehrmann, L.; Golden, R.L.; Naraparaju, K.; Croucher, J.L.; MacFarland, S.P.; Guan, P.; Kolla, V.; Wei, G.; Cam, N.; Li, G.; Hornby, Z.; Brodeur, G.M. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett., 2016, 372(2), 179-186.
[http://dx.doi.org/10.1016/j.canlet.2016.01.018] [PMID: 26797418]
[56]
Roskoski, R., Jr ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. Pharmacol. Res., 2017, 121, 202-212.
[http://dx.doi.org/10.1016/j.phrs.2017.04.022] [PMID: 28465216]
[57]
Roskoski, R. Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Pharmacol. Res., 2020, 152(152)104609
[http://dx.doi.org/10.1016/j.phrs.2019.104609] [PMID: 31862477]
[58]
Rozlytrek (entrectinib) capsules: Japanese prescribing information. 2019. Available from: http://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/450045_42910
[59]
Drilon, A.; Siena, S.; Ou, S.I.; Patel, M.; Ahn, M.J.; Lee, J.; Bauer, T.M.; Farago, A.F.; Wheler, J.J.; Liu, S.V.; Doebele, R.; Giannetta, L.; Cerea, G.; Marrapese, G.; Schirru, M.; Amatu, A.; Bencardino, K.; Palmeri, L.; Sartore-Bianchi, A.; Vanzulli, A.; Cresta, S.; Damian, S.; Duca, M.; Ardini, E.; Li, G.; Christiansen, J.; Kowalski, K.; Johnson, A.D.; Patel, R.; Luo, D.; Chow-Maneval, E.; Hornby, Z.; Multani, P.S.; Shaw, A.T.; De Braud, F.G. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: Combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov., 2017, 7(4), 400-409.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1237] [PMID: 28183697]
[60]
Meneses-Lorente, G.; Bentley, D.; Guerini, E.; Kowalski, K.; Chow-Maneval, E.; Yu, L.; Brink, A.; Djebli, N.; Mercier, F.; Buchheit, V.; Phipps, A. Characterization of the pharmacokinetics of entrectinib and its active M5 metabolite in healthy volunteers and patients with solid tumors. Invest. New Drugs, 2021, 39(3), 803-811.
[http://dx.doi.org/10.1007/s10637-020-01047-5] [PMID: 33462752]
[61]
Parrott, N.; Stillhart, C.; Lindenberg, M.; Wagner, B.; Kowalski, K.; Guerini, E.; Djebli, N.; Meneses-Lorente, G. Physiologically based absorption modelling to explore the impact of food and gastric pH changes on the pharmacokinetics of entrectinib. AAPS J., 2020, 22(4), 78.
[http://dx.doi.org/10.1208/s12248-020-00463-y] [PMID: 32458089]
[62]
Tan, D.; Antoniou, M.; Zerbini, C.H. PRO41 the economic and quality of life impact of entrectinib on CNS metastasis control. Value Health, 2021, 24, 204-205.
[63]
Fischer, H.; Ullah, M.; de la Cruz, C.C.; Hunsaker, T.; Senn, C.; Wirz, T.; Wagner, B.; Draganov, D.; Vazvaei, F.; Donzelli, M.; Paehler, A.; Merchant, M.; Yu, L. Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein. Neuro-oncol., 2020, 22(6), 819-829.
[http://dx.doi.org/10.1093/neuonc/noaa052] [PMID: 32383735]
[64]
Cruz, C.C.; Hunsaker, T.; Vazvaei, F.; Draganov, D.; Yu, L.; Merchant, M. Abstract 3894: Determination of the efficacious Entrectinib exposures required for pathway inhibition and anti-tumor activity in a subcutaneous and intracranial TPM3-NTRK1 mutant tumor model. Cancer Res., 2019, 79(13), 3894-3894.
[65]
Frampton, J.E. Entrectinib: A Review in NTRK+ Solid Tumours and ROS1+ NSCLC. Drugs, 2021, 81(6), 697-708.
[http://dx.doi.org/10.1007/s40265-021-01503-3] [PMID: 33871816]
[66]
Chu, P.; Batson, S.; Hodgson, M.; Mitchell, C.R.; Steenrod, A. Systematic review of neurotrophic tropomyosin-related kinase inhibition as a tumor-agnostic management strategy. Future Oncol., 2020, 16(4), 61-74.
[http://dx.doi.org/10.2217/fon-2019-0534] [PMID: 31942815]
[67]
Chu, P.; Antoniou, M.; Bhutani, M.K.; Aziez, A.; Daigl, M. Matching-adjusted indirect comparison: entrectinib versus crizotinib in ROS1 fusion-positive non-small cell lung cancer. J. Comp. Eff. Res., 2020, 9(12), 861-876.
[http://dx.doi.org/10.2217/cer-2020-0063] [PMID: 32648475]
[68]
Doebele, R.; Perez, L.; Trinh, H.; Martinec, M.; Martina, R.; Riehl, T. P1.01-83 comparative efficacy analysis between entrectinib trial and crizotinib Real-World ROS1 fusion-positive (ROS1+) NSCLC patients. J. Thorac. Oncol., 2019, 14(10), S392.
[http://dx.doi.org/10.1016/j.jtho.2019.08.798]
[69]
Attwa, M.W.; Darwish, H.W.; Alhazmi, H.A.; Kadi, A.A. Investigation of metabolic degradation of new ALK inhibitor: Entrectinib by LC-MS/MS. Clin. Chim. Acta, 2018, 485, 298-304.
[http://dx.doi.org/10.1016/j.cca.2018.07.009] [PMID: 30006284]
[70]
Attwa, M.W.; Kadi, A.A.; Alrabiah, H.; Darwish, H.W. LC-MS/MS reveals the formation of iminium and quinone methide reactive intermediates in entrectinib metabolism: In vivo and in vitro metabolic investigation. J. Pharm. Biomed. Anal., 2018, 160, 19-30.
[http://dx.doi.org/10.1016/j.jpba.2018.07.032] [PMID: 30055343]
[71]
Ma, S.; Zhu, M. Recent advances in applications of liquid chromatography-tandem mass spectrometry to the analysis of reactive drug metabolites. Chem. Biol. Interact., 2009, 179(1), 25-37.
[http://dx.doi.org/10.1016/j.cbi.2008.09.014] [PMID: 18848531]
[72]
KK S.; SV, L. STARTRK-2: A global phase 2, open-label, basket study of entrectinib in patients with locally advanced or metastatic solid tumors harboring TRK, ROS1, or ALK gene fusions. Cancer Res., 2017, 77(615)
[73]
Demetri, G.D.; Paz-Ares, L.; Farago, A.F.; Liu, S.V.; Chawla, S.P.; Tosi, D. Efficacy and safety of entrectinib in patients with NTRK fusion- positive (NTRK-fp) Tumors: Pooled analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. Ann. Oncol., 2018, 29(Suppl. 8), 424-017.
[74]
Abdulla, D.; Doebele, R.; Ahn, M.; Siena, S.; Drilon, A.; Krebs, M. ENCORE: Efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC). Pneumologie, 2019, 73(01), 623.
[75]
Drilon, A.; Siena, S.; Dziadziuszko, R.; Barlesi, F.; Krebs, M.G.; Shaw, A.T.; de Braud, F.; Rolfo, C.; Ahn, M.J.; Wolf, J.; Seto, T.; Cho, B.C.; Patel, M.R.; Chiu, C.H.; John, T.; Goto, K.; Karapetis, C.S.; Arkenau, H.T.; Kim, S.W.; Ohe, Y.; Li, Y.C.; Chae, Y.K.; Chung, C.H.; Otterson, G.A.; Murakami, H.; Lin, C.C.; Tan, D.S.W.; Prenen, H.; Riehl, T.; Chow-Maneval, E.; Simmons, B.; Cui, N.; Johnson, A.; Eng, S.; Wilson, T.R.; Doebele, R.C. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol., 2020, 21(2), 261-270.
[http://dx.doi.org/10.1016/S1470-2045(19)30690-4] [PMID: 31838015]
[76]
Rolfo, C.D.; De Braud, F.G.; Doebele, R.C.; Drilon, A.E.; Siena, S.; Patel, M. Efficacy and safety of entrectinib in patients (pts) with NTRK-fusion positive (NTRK-fp) solid tumors: An updated integrated analysis. J. Clin. Oncol., 2020, 38(15), 3605.
[77]
Desai, A.V.; Brodeur, G.M.; Foster, J.; Berg, S.L.; Basu, E.M.; Shusterman, S. Phase 1 study of entrectinib (RXDX-101), a TRK, ROS1, and ALK inhibitor, in children, adolescents, and young adults with recurrent or refractory solid tumors. J. Clin. Oncol., 2018, 36(15), 10536.
[78]
Robinson, G.W.; Gajjar, A.J.; Gauvain, K.M.; Basu, E.M.; Macy, M.E.; Maese, L.D. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. J. Clin. Oncol., 2019, 37(15), 1009.
[79]
Desai, A.V.; Robinson, G.W.; Basu, E.M.; Foster, J.; Gauvain, K.; Sabnis, A. Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors, including primary CNS tumors. J. Clin. Oncol., 2020, 38(15), 107.
[http://dx.doi.org/10.1200/JCO.2020.38.15_suppl.107]
[80]
ClinicalTrials.gov. A study to evaluate efficacy and safety of multiple targeted therapies as treatments for participants with non-small cell lung cancer (NSCLC) (B-FAST). 2017. Available from: https://www.clinicaltrials. gov/ct2/show/NCT03178552?id=NCT03178552&draw=2&rank=1# moreinfo
[81]
ClinicalTrials.gov. A study to investigate the relative bioavailability of entrectinib capsule formulations F1 and F06 under fed conditions in healthy participants. 2019. Available from: https://www.clinicaltrials.gov/ct2/show/NCT037
[82]
ClinicalTrials.gov. A performance and bioavailability study of entrectinib in healthy volunteers. 2019. Available from: https://www.clinicaltrials.gov/ct2/show/NCT0396 11 00? id=NCT03961100&draw=2&rank=1
[83]
Dziadziuszko, R.; Krebs, M.G.; De Braud, F.; Siena, S.; Drilon, A.; Doebele, R.C.; Patel, M.R.; Cho, B.C.; Liu, S.V.; Ahn, M.J.; Chiu, C.H.; Farago, A.F.; Lin, C.C.; Karapetis, C.S.; Li, Y.C.; Day, B.M.; Chen, D.; Wilson, T.R.; Barlesi, F. Updated integrated analysis of the efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small-cell lung cancer. J. Clin. Oncol., 2021, 39(11), 1253-1263.
[http://dx.doi.org/10.1200/JCO.20.03025] [PMID: 33646820]
[84]
Russo, M.; Misale, S.; Wei, G.; Siravegna, G.; Crisafulli, G.; Lazzari, L.; Corti, G.; Rospo, G.; Novara, L.; Mussolin, B.; Bartolini, A.; Cam, N.; Patel, R.; Yan, S.; Shoemaker, R.; Wild, R.; Di Nicolantonio, F.; Bianchi, A.S.; Li, G.; Siena, S.; Bardelli, A. Acquired resistance to the TRK inhibitor entrectinib in colorectal cancer. Cancer Discov., 2016, 6(1), 36-44.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0940] [PMID: 26546295]
[85]
Zou, H.Y.; Friboulet, L.; Kodack, D.P.; Engstrom, L.D.; Li, Q.; West, M.; Tang, R.W.; Wang, H.; Tsaparikos, K.; Wang, J.; Timofeevski, S.; Katayama, R.; Dinh, D.M.; Lam, H.; Lam, J.L.; Yamazaki, S.; Hu, W.; Patel, B.; Bezwada, D.; Frias, R.L.; Lifshits, E.; Mahmood, S.; Gainor, J.F.; Affolter, T.; Lappin, P.B.; Gukasyan, H.; Lee, N.; Deng, S.; Jain, R.K.; Johnson, T.W.; Shaw, A.T.; Fantin, V.R.; Smeal, T. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell, 2015, 28(1), 70-81.
[http://dx.doi.org/10.1016/j.ccell.2015.05.010] [PMID: 26144315]
[86]
Friboulet, L.; Li, N.; Katayama, R.; Lee, C.C.; Gainor, J.F.; Crystal, A.S.; Michellys, P.Y.; Awad, M.M.; Yanagitani, N.; Kim, S.; Pferdekamper, A.C.; Li, J.; Kasibhatla, S.; Sun, F.; Sun, X.; Hua, S.; McNamara, P.; Mahmood, S.; Lockerman, E.L.; Fujita, N.; Nishio, M.; Harris, J.L.; Shaw, A.T.; Engelman, J.A. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov., 2014, 4(6), 662-673.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0846] [PMID: 24675041]
[87]
Katayama, R.; Friboulet, L.; Koike, S.; Lockerman, E.L.; Khan, T.M.; Gainor, J.F.; Iafrate, A.J.; Takeuchi, K.; Taiji, M.; Okuno, Y.; Fujita, N.; Engelman, J.A.; Shaw, A.T. Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin. Cancer Res., 2014, 20(22), 5686-5696.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1511] [PMID: 25228534]
[88]
Ku, B.M.; Bae, Y.H.; Lee, K.Y.; Sun, J.M.; Lee, S.H.; Ahn, J.S.; Park, K.; Ahn, M.J. Entrectinib resistance mechanisms in ROS1-rearranged non-small cell lung cancer. Invest. New Drugs, 2020, 38(2), 360-368.
[http://dx.doi.org/10.1007/s10637-019-00795-3] [PMID: 31124056]
[89]
Doebele, R.C.; Dziadziuszko, R.; Drilon, A.; Shaw, A.; Wolf, J.; Farago, A.F. Genomic landscape of entrectinib resistance from ctDNA analysis in STARTRK-2. Ann. Oncol., 2019, 30(October), v865.
[http://dx.doi.org/10.1093/annonc/mdz394.017]
[90]
Gainor, J.F.; Tseng, D.; Yoda, S.; Dagogo-Jack, I.; Friboulet, L.; Lin, J.J. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer. JCO Precis Oncol., 2017, 2017(1), 1-13.

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