Inetetamab in Combination With Pyrotinib in HER2 Mutant or Amplified Advanced Non-small Cell Lung Cancer

Summary

This is a Phase 1, open-label study to evaluate the safety and the efficacy of inetetamab in combination with pyrotinib in patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer

Timeline

Start

2021-07-28

Primary completion

2023-08-01

Completion

2025-02-01

Publications

• Results Cocco E, Lopez S, Santin AD, Scaltriti M. Prevalence and role of HER2 mutations in cancer. Pharmacol Ther. 2019 Jul;199:188-196. doi: 10.1016/j.pharmthera.2019.03.010. Epub 2019 Apr 2.
• Results Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol. 2005 May 10;23(14):3270-8. doi: 10.1200/JCO.2005.11.478.
• Results Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815.
• Results Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, Stevens C, O'Meara S, Smith R, Parker A, Barthorpe A, Blow M, Brackenbury L, Butler A, Clarke O, Cole J, Dicks E, Dike A, Drozd A, Edwards K, Forbes S, Foster R, Gray K, Greenman C, Halliday K, Hills K, Kosmidou V, Lugg R, Menzies A, Perry J, Petty R, Raine K, Ratford L, Shepherd R, Small A, Stephens Y, Tofts C, Varian J, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Knowles M, Leung SY, Louis DN, Looijenga LH, Malkowicz B, Pierotti MA, Teh B, Chenevix-Trench G, Weber BL, Yuen ST, Harris G, Goldstraw P, Nicholson AG, Futreal PA, Wooster R, Stratton MR. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature. 2004 Sep 30;431(7008):525-6. doi: 10.1038/431525b.
• Results Arcila ME, Chaft JE, Nafa K, Roy-Chowdhuri S, Lau C, Zaidinski M, Paik PK, Zakowski MF, Kris MG, Ladanyi M. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012 Sep 15;18(18):4910-8. doi: 10.1158/1078-0432.CCR-12-0912. Epub 2012 Jul 3.
• Results Gatzemeier U, Groth G, Butts C, Van Zandwijk N, Shepherd F, Ardizzoni A, Barton C, Ghahramani P, Hirsh V. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol. 2004 Jan;15(1):19-27. doi: 10.1093/annonc/mdh031.
• Results Lara PN Jr, Laptalo L, Longmate J, Lau DH, Gandour-Edwards R, Gumerlock PH, Doroshow JH, Gandara DR; California Cancer Consortium. Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a California Cancer Consortium screening and phase II trial. Clin Lung Cancer. 2004 Jan;5(4):231-6. doi: 10.3816/clc.2004.n.004.
• Results Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):474-9. doi: 10.1073/pnas.0808930106. Epub 2009 Jan 2.
• Results Shimamura T, Ji H, Minami Y, Thomas RK, Lowell AM, Shah K, Greulich H, Glatt KA, Meyerson M, Shapiro GI, Wong KK. Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer Res. 2006 Jul 1;66(13):6487-91. doi: 10.1158/0008-5472.CAN-06-0971.
• Results Kris MG, Camidge DR, Giaccone G, Hida T, Li BT, O'Connell J, Taylor I, Zhang H, Arcila ME, Goldberg Z, Janne PA. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol. 2015 Jul;26(7):1421-7. doi: 10.1093/annonc/mdv186. Epub 2015 Apr 21.
• Results Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013 Jun 1;31(16):1997-2003. doi: 10.1200/JCO.2012.45.6095. Epub 2013 Apr 22.
• Results De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.
• Results Diaz R, Nguewa PA, Parrondo R, Perez-Stable C, Manrique I, Redrado M, Catena R, Collantes M, Penuelas I, Diaz-Gonzalez JA, Calvo A. Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model. BMC Cancer. 2010 May 11;10:188. doi: 10.1186/1471-2407-10-188.
• Results Wang Y, Jiang T, Qin Z, Jiang J, Wang Q, Yang S, Rivard C, Gao G, Ng TL, Tu MM, Yu H, Ji H, Zhou C, Ren S, Zhang J, Bunn P, Doebele RC, Camidge DR, Hirsch FR. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol. 2019 Mar 1;30(3):447-455. doi: 10.1093/annonc/mdy542.
• Results Zhou C, Li X, Wang Q, Gao G, Zhang Y, Chen J, Shu Y, Hu Y, Fan Y, Fang J, Chen G, Zhao J, He J, Wu F, Zou J, Zhu X, Lin X. Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2020 Aug 20;38(24):2753-2761. doi: 10.1200/JCO.20.00297. Epub 2020 Jul 2.

Drugs

Indications