Etirinotecan pegol (NKTR-102)
|Etirinotecan pegol (NKTR-102)
||Metastatic Breast Cancer
||Platinum-Resistant Ovarian Cancer
||Second-Line Colorectal Cancer
||GI and solid tumors
In combination with 5-FU
Etirinotecan pegol is in Phase 3 clinical development for patients with metastatic breast cancer and Phase 2 clinical development for patients with solid tumor malignancies, including ovarian and colorectal cancers. Each year, approximately 3 million patients worldwide are diagnosed with one of these types of cancer.
Erinotecan Pegol Clinical Data and Product Profile
Etirinotecan pegol is a next generation topoisomerase I-inhibitor with a unique pharmacokinetics profile that provides a continuous concentration of active drug with reduced peak concentrations. Etirinotecan pegol was invented by Nektar using its polymer conjugate technology platform which conjugates cytotoxic small molecules to a uniquely engineered macromolecular polymer core using specialized linkers.
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 macromolecular 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 with etirinotecan pegol have been shown to increase the life and exposure profiles relative to irinotecan, resulting in significant anti-tumor activity. In preclinical models, etirinotecan pegol achieved a 300-fold increase in tumor concentration as compared to a first generation topo 1 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.
Clinical studies have shown that the half-life of active drug generated from etirinotecan pegol is greatly extended to 50 days and that active drug remains in circulation throughout the entire chemotherapy cycle, providing sustained exposure to topo I inhibition.
Etirinotecan pegol is currently in development for the treatment of breast, ovarian and colorectal cancers.
Ongoing clinical development for etirinotecan pegol:
- In metastatic breast cancer, a Phase 3 randomized, head to head study of etirinotecan pegol compared to Treatment of Physician's Choice (TPC) is currently enrolling.
- In ovarian cancer, an expanded Phase 2 study of single-agent etirinotecan pegol in platinum refractory/resistant ovarian cancer in women who failed prior Doxil therapy completed enrollment of approximately 170 patients in total. The study is ongoing and is expected to be completed by the end of 2012.
- In colorectal cancer, a 174-patient Phase 2 randomized, head-to-head study of etirinotecan pegol compared to irinotecan in patients with second-line colorectal cancer with the KRAS gene mutation is in progress, along with a Phase 1 study to explore the use of etirinotecan pegol in a combination regimen with 5-FU based therapy.
Highlighted Data Presentations:
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 etirinotecan pegol in metastatic breast cancer were presented at the 2011 ASCO Annual meeting (click here to download this presentation). 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 (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 (click here to download this presentation).
Data from a Phase 2 clinical study of etirinotecan pegol in platinum-resistant/refractory ovarian cancer were presented at the 2010 ASCO Meeting (click here to download this presentation).
|September 7-9, 2013
||ASCO 2013 Breast Cancer Symposium
||San Francisco, CA|
|September 26-29, 2013
||15th Annual Lynn Sage Breast Cancer Symposium
|September 27 - October 1, 2013
||ECCO-ESMO-ESTRO European Cancer Congress
|October 19-23, 2013
|November 5-9, 2013
||Chemotherapy Foundation Symposium
||New York, NY|
|November 9-13, 2013
||Society for Neuroscience: Neuroscience
||San Diego, CA|
|November 21-24, 2013
||4th Quadrennial Meeting of the World Federation of Neuro-Oncology
||San Francisco, CA|
|December 10-14, 2013
||San Antonio Breast Cancer Symposium
||San Antonio, TX|
View our Scientific & Medical event calendar »