MedKoo product information:

NKTR102

pegylated irinotecan NKTR 102 is a formulation of polyethylene glycol (PEG)-encapsulated irinotecan with antineoplastic activity. The prodrug irinotecan, a semisynthetic derivative of camptothecin, is converted to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, 7-ethyl-10-hydroxy-camptothecin inhibits topoisomerase I activity by stabilizing the cleavable complex of topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptosis. Pegylation provides improved drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic effects while lowering the toxicity profile. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

NKTR-102 is currently being developed by Nektar. According to the company's news release, this agent exhibits a very high response rate and excellent clinical benefit rate in patients with metastatic breast cancer, and importantly, this anti-tumor activity is maintained in each of the poor prognosis subsets within the study. The data from the Phase 2 study also shows highly promising PFS of 5.3 months and OS of 13.1 months in the every three week dose schedule, which was also very well-tolerated.   As a novel topoisomerase I inhibitor in breast cancer, NKTR-102 holds great therapeutic potential and allows us to address the challenge of resistance in this setting.

Current developer:    Nektar Therapeutics.

1: Iwase Y, Maitani Y. Dual functional octreotide-modified liposomal irinotecan leads to high therapeutic efficacy for medullary thyroid carcinoma xenografts. Cancer Sci. 2011 Oct 24. doi: 10.1111/j.1349-7006.2011.02128.x. [Epub ahead of print] PubMed PMID: 22017398.

2: Matsuzaki T, Takagi A, Furuta T, Ueno S, Kurita A, Nohara G, Kodaira H, Sawada S, Hashimoto S. Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models. Oncol Rep. 2012 Jan;27(1):189-97. doi: 10.3892/or.2011.1465. Epub 2011 Sep 20. PubMed PMID: 21935577.

3: Cobleigh MA. Other options in the treatment of advanced breast cancer. Semin Oncol. 2011 Jun;38 Suppl 2:S11-6. Review. PubMed PMID: 21600380.

4: Li C, Cui J, Wang C, Li Y, Zhang L, Xiu X, Li Y, Wei N, Zhang L, Wang P. Novel sulfobutyl ether cyclodextrin gradient leads to highly active liposomal irinotecan formulation. J Pharm Pharmacol. 2011 Jun;63(6):765-73. doi: 10.1111/j.2042-7158.2011.01272.x. Epub 2011 Apr 7. PubMed PMID: 21585373.

5: Iwase Y, Maitani Y. Octreotide-targeted liposomes loaded with CPT-11 enhanced cytotoxicity for the treatment of medullary thyroid carcinoma. Mol Pharm. 2011 Apr 4;8(2):330-7. Epub 2011 Jan 18. PubMed PMID: 21166471.

6: Xenidis N, Vardakis N, Varthalitis I, Giassas S, Kontopodis E, Ziras N, Gioulbasanis I, Samonis G, Kalbakis K, Georgoulias V. Α multicenter phase II study of pegylated liposomal doxorubicin in combination with irinotecan as second-line treatment of patients with refractory small-cell lung cancer. Cancer Chemother Pharmacol. 2011 Jul;68(1):63-8. Epub 2010 Sep 10. PubMed PMID: 20830475.

7: Pastorino F, Loi M, Sapra P, Becherini P, Cilli M, Emionite L, Ribatti D, Greenberger LM, Horak ID, Ponzoni M. Tumor regression and curability of preclinical neuroblastoma models by PEGylated SN38 (EZN-2208), a novel topoisomerase I inhibitor. Clin Cancer Res. 2010 Oct 1;16(19):4809-21. Epub 2010 Aug 11. PubMed PMID: 20702613.

8: Morgensztern D, Baggstrom MQ, Pillot G, Tan B, Fracasso P, Suresh R, Wildi J, Govindan R. A phase I study of pegylated liposomal doxorubicin and irinotecan in patients with solid tumors. Chemotherapy. 2009;55(6):441-5. Epub 2009 Dec 8. PubMed PMID: 19996589.

9: Meckley LM, Neumann PJ. Personalized medicine: factors influencing reimbursement. Health Policy. 2010 Feb;94(2):91-100. Epub 2009 Oct 7. PubMed PMID: 19815307.

10: Skak K, Søndergaard H, Frederiksen KS, Ehrnrooth E. In vivo antitumor efficacy of interleukin-21 in combination with chemotherapeutics. Cytokine. 2009 Dec;48(3):231-8. Epub 2009 Aug 25. PubMed PMID: 19709902.

11: Murphy CG, Seidman AD. Evolving approaches to metastatic breast cancer previously treated with anthracyclines and taxanes. Clin Breast Cancer. 2009 Jun;9 Suppl 2:S58-65. Review. PubMed PMID: 19596644.

12: Fox ME, Guillaudeu S, Fréchet JM, Jerger K, Macaraeg N, Szoka FC. Synthesis and in vivo antitumor efficacy of PEGylated poly(l-lysine) dendrimer-camptothecin conjugates. Mol Pharm. 2009 Sep-Oct;6(5):1562-72. PubMed PMID: 19588994; PubMed Central PMCID: PMC2765109.

13: Atyabi F, Farkhondehfai A, Esmaeili F, Dinarvand R. Preparation of pegylated nano-liposomal formulation containing SN-38: In vitro characterization and in vivo biodistribution in mice. Acta Pharm. 2009 Jun;59(2):133-44. PubMed PMID: 19564139.

14: Liu Z, Robinson JT, Sun X, Dai H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc. 2008 Aug 20;130(33):10876-7. Epub 2008 Jul 29. PubMed PMID: 18661992; PubMed Central PMCID: PMC2597374.

15: Scott LC, Yao JC, Benson AB 3rd, Thomas AL, Falk S, Mena RR, Picus J, Wright J, Mulcahy MF, Ajani JA, Evans TR. A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. Cancer Chemother Pharmacol. 2009 Jan;63(2):363-70. Epub 2008 Apr 9. PubMed PMID: 18398613.

16: Almubarak M, Newton M, Altaha R. Reinduction of bevacizumab in combination with pegylated liposomal Doxorubicin in a patient with recurrent glioblastoma multiforme who progressed on bevacizumab/irinotecan. J Oncol. 2008;2008:942618. Epub 2008 Sep 2. PubMed PMID: 19259336; PubMed Central PMCID: PMC2648641.

17: Krauze MT, Noble CO, Kawaguchi T, Drummond D, Kirpotin DB, Yamashita Y, Kullberg E, Forsayeth J, Park JW, Bankiewicz KS. Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts. Neuro Oncol. 2007 Oct;9(4):393-403. Epub 2007 Jul 24. PubMed PMID: 17652269; PubMed Central PMCID: PMC1994096.

18: Li YF, Fu S, Hu W, Liu JH, Finkel KW, Gershenson DM, Kavanagh JJ. Systemic anticancer therapy in gynecological cancer patients with renal dysfunction. Int J Gynecol Cancer. 2007 Jul-Aug;17(4):739-63. Epub 2007 Feb 16. Review. PubMed PMID: 17309673.

19: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Dec;28(10):719-40. PubMed PMID: 17235418.

20: Lokich J. Same-day pegfilgrastim and chemotherapy. Cancer Invest. 2005;23(7):573-6. PubMed PMID: 16305982.

21: Honig A, Rieger L, Sutterlin A, Kapp M, Dietl J, Sutterlin MW, Kämmerer U. Brain metastases in breast cancer--an in vitro study to evaluate new systemic chemotherapeutic options. Anticancer Res. 2005 May-Jun;25(3A):1531-7. PubMed PMID: 16033055.