Etirinotecan pegol (NKTR-102)

Therapeutic Area Nektar
Discovered
Indication Phase
Oncology  
Etirinotecan pegol (NKTR-102)
Metastatic Breast Cancer
Phase 3
Platinum-Resistant Ovarian Cancer
Phase 2 Completed
Second-Line Colorectal Cancer
Phase 2 Completed
Bevacizumab (Avastin)-refractory high-grade glioma
Phase 2 Completed
Non-Small Cell Lung Cancer (NSCLC)
Phase 2 Completed
Small Cell Lung Cancer (SCLC)
Phase 2 Completed
GI and solid tumors
In combination with 5-FU

Phase 1 Completed

Etirinotecan Pegol Clinical Data and Product Profile

Etirinotecan pegol (NKTR-102) is the first long-acting topoisomerase I-inhibitor (Topo I) designed to concentrate in tumor tissue, provide sustained tumor suppression throughout the entire chemotherapy cycle, and to reduce the peak exposures that are associated with toxicities of other cytotoxics. Etirinotecan pegol was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar's releasable polymer technology platform.

Topo I-inhibitors are important chemotherapeutic agents used to treat cancer. Immediately after dosing, however, standard topo I-inhibitors reach high peak concentrations and diffuse quickly throughout the body---penetrating and damaging healthy tissue, such as bone marrow, as well as tumor tissue. Subsequent rapid metabolism limits topo I exposure in tumor cells, reducing the duration of their effect and resulting in a much lower tumor exposure to the active metabolite that may limit their efficacy.

Etirinotecan pegol is a novel chemotherapeutic designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities. Unlike first generation topo I-inhibitors that exhibit a high initial peak concentration and short half-life, etirinotecan pegol's unique pro-drug design results in a lowered initial peak concentration of active topo I inhibitor in the blood. The large etirinotecan pegol molecule is inactive when administered. Over time, the body's natural enzymatic processes slowly metabolize the linkers within the molecule, continuously freeing active drug that then works to stop tumor cell division through inhibition of topo I.

Clinical and preclinical studies have shown that the half-life of active drug generated from etirinotecan pegol is greatly extended to 50 days (compared to 48 hours for irinotecan) and that active drug remains in circulation throughout the entire chemotherapy cycle, providing sustained exposure to topo I inhibition. In preclinical models, etirinotecan pegol achieved a 300-fold increase in tumor concentration as compared to a first generation topo I-inhibitor. Because etirinotecan pegol is a large molecule, it is believed to penetrate the leaky vasculature within the tumor environment more readily than normal vasculature, concentrating and trapping etirinotecan pegol in tumor tissue.

Highlighted Data Presentations:

Data from a Phase 2 clinical study of etirinotecan pegol in metastatic breast cancer were published in the November 2013 issue of The Lancet Oncology (click here to view manuscript) These data were previously presented at the 2011 ASCO Annual meeting (click here to download this presentation).

Data from a Phase 2 clinical study of etirinotecan pegol in platinum-resistant/refractory ovarian cancer were published in the September 30, 2013 online edition of the Journal of Clinical Oncology (click here to view abstract). These data were previously presented at the 2010 ASCO Meeting (click here to download this presentation).

Data from a Phase 2 clinical study of etirinotecan pegol in metastatic breast cancer were presented in an oral abstract session at the 2011 ASCO Breast Cancer Symposium by Agustin Garcia, MD. View presentation slides.

Data from a Phase 2 clinical study of NKTR-102 in a subpopulation of patients with platinum-resistant/refractory ovarian cancer and prior Doxil® (pegylated liposomal doxorubicin or PLD) treatment were presented at the 2011 ASCO Annual Meeting by Agustin Garcia, MD. (click here to download this presentation).

Data from a Phase 2 clinical study of etirinotecan pegol in metastatic breast cancer were presented at the 2010 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium by Amad Awada, MD. (click here to download this presentation).

February 14, 2016 26.2 with Donna - Breast Cancer Marathon Jacksonville, FL
April 16-20, 2016 AACR Annual Meeting 2016 New Orleans, LA
June 3-9, 2016 2016 ASCO Annual Meeting Chicago, IL
December 6-10, 2016 San Antonio Breast Cancer Symposium San Antonio, TX

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