Motesanib Explained

Motesanib (AMG 706) is an experimental drug candidate originally developed by Amgen[1] but later investigated by the Takeda Pharmaceutical Company. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of VEGF receptors, platelet-derived growth factor receptors, and stem cell factor receptors.[2] It is used as the phosphate salt motesanib diphosphate. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda.[3]

Clinical trials

Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), with Phase II trials indicating an effectiveness comparable to bevacizumab when they were both used in combination with paclitaxel/carboplatin.[4] However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC.[2] [5] A second Phase III trial was started in 2012,[6] which focused on patients from Asian backgrounds (performed on the basis of subgroup analysis)[7] however this also failed to meet its primary endpoint.[8]

The drug has undergone a Phase II evaluation as first-line therapy for breast cancer[2] however this study found no evidence to support further investigation.[9] Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful.[10] Two phase II clinical trials for thyroid cancer showed promising results.[11] [12] [13]

External links

Notes and References

  1. Book: Stafford. edited by Rongshi Li, Jeffrey A.. Kinase inhibitor drugs. limited. 2009. Wiley. Hoboken, N.J.. 978-0-470-27829-1. 113–130. Chapter 5. Discovery of Motesanib. 10.1002/9780470524961.ch5.
  2. News: Amgen and Takeda's NSCLC Drug Fails in Phase III Study . 30 Mar 2011 .
  3. Web site: Motesanib. AdisInsight. 1 February 2017.
  4. Blumenschein Jr. G. R.. Kabbinavar. F.. Menon. H.. Mok. T. S. K.. Stephenson. J.. Beck. J. T.. Lakshmaiah. K.. Reckamp. K.. Hei. Y.- J.. Kracht. K.. Sun. Y.- N.. Sikorski. R.. Schwartzberg. L.. A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Annals of Oncology. 14 February 2011. 22. 9. 2057–2067. 10.1093/annonc/mdq731. 21321086. free.
  5. Scagliotti. G. V.. Vynnychenko. I.. Park. K.. Ichinose. Y.. Kubota. K.. Blackhall. F.. Pirker. R.. Galiulin. R.. Ciuleanu. T.-E.. Sydorenko. O.. Dediu. M.. Papai-Szekely. Z.. Banaclocha. N. M.. McCoy. S.. Yao. B.. Hei. Y.-j.. Galimi. F.. Spigel. D. R.. International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer: MONET1. Journal of Clinical Oncology. 2 July 2012. 30. 23. 2829–2836. 10.1200/JCO.2011.41.4987. 22753922. 2318/118283. free.
  6. Web site: Takeda Initiates Phase 3 Trial of Motesanib in Japan and Additional Asian Countries. Takeda Pharmaceutical Company Limited. 19 February 2015.
  7. Kubota. K.. Ichinose. Y.. Scagliotti. G.. Spigel. D.. Kim. J. H.. Shinkai. T.. Takeda. K.. Kim. S.- W.. Hsia. T.- C.. Li. R. K.. Tiangco. B. J.. Yau. S.. Lim. W.- T.. Yao. B.. Hei. Y.- J.. Park. K.. Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis. Annals of Oncology. 13 January 2014. 25. 2. 529–536. 10.1093/annonc/mdt552. 24419239. free. 2318/150328. free.
  8. Web site: Takeda Announces Phase 3 MONET-A Study Evaluating Motesanib (AMG 706) in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer Does Not Meet Primary Endpoint. Takeda Pharmaceutical Company Limited. 19 February 2015.
  9. Martin. Miguel. Roche. Henri. Pinter. Tamas. Crown. John. Kennedy. M John. Provencher. Louise. Priou. Frank. Eiermann. Wolfgang. Adrover. Encarna. Lang. Istvan. Ramos. Manuel. Latreille. Jean. Jagiełło-Gruszfeld. Agnieszka. Pienkowski. Tadeusz. Alba. Emilio. Snyder. Raymond. Almel. Sachin. Rolski. Janusz. Munoz. Montserrat. Moroose. Rebecca. Hurvitz. Sara. Baños. Ana. Adewoye. Henry. Hei. Yong-Jiang. Lindsay. Mary-Ann. Rupin. Matthieu. Cabaribere. David. Lemmerick. Yasmin. Mackey. John R. Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study. The Lancet Oncology. April 2011. 12. 4. 369–376. 10.1016/S1470-2045(11)70037-7. 21429799.
  10. Schilder. R.J.. Sill. M.W.. Lankes. H.A.. Gold. M.A.. Mannel. R.S.. Modesitt. S.C.. Hanjani. P.. Bonebrake. A.J.. Sood. A.K.. Godwin. A.K.. Hu. W.. Alpaugh. R.K.. A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: A Gynecologic Oncology Group study. Gynecologic Oncology. April 2013. 129. 1. 86–91. 10.1016/j.ygyno.2013.01.006. 23321064. 3712785.
  11. http://news.cancerconnect.com/motesanib-diphosphate-provides-anticancer-activity-among-patients-with-progressive-thyroid-cancer/ Motesanib Diphosphate Provides Anticancer Activity Among Patients with Progressive Thyroid Cancer
  12. Schlumberger. M. J.. Elisei. R.. Bastholt. L.. Wirth. L. J.. Martins. R. G.. Locati. L. D.. Jarzab. B.. Pacini. F.. Daumerie. C.. Droz. J.-P.. Eschenberg. M. J.. Sun. Y.-N.. Juan. T.. Stepan. D. E.. Sherman. S. I.. Phase II Study of Safety and Efficacy of Motesanib in Patients With Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer. Journal of Clinical Oncology. 29 June 2009. 27. 23. 3794–3801. 10.1200/JCO.2008.18.7815. 19564535. free.
  13. Sherman. Steven I.. Wirth. Lori J.. Droz. Jean-Pierre. Hofmann. Michael. Bastholt. Lars. Martins. Renato G.. Licitra. Lisa. Eschenberg. Michael J.. Sun. Yu-Nien. Juan. Todd. Stepan. Daniel E.. Schlumberger. Martin J.. Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer. New England Journal of Medicine. 3 July 2008. 359. 1. 31–42. 10.1056/NEJMoa075853. 18596272. 2318/100325. free.

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