Onzeald (etirinotecan pegol)

ONZEALD (etirinotecan pegol)

Indication: Advanced breast cancer and brain metastases

Discovered and wholly owned by Nektar


Phase 3

ONZEALD (etirinotecan pegol) Clinical Data and Profile

A diagnosis of brain metastases in women with advanced breast cancer is devastating and there are no therapies approved to treat this specific patient population. In fact, the incidence of breast cancer brain metastases is between 10-30 percent.1 Breast cancer is the most frequently diagnosed cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.2 There are approximately 250,000 newly-diagnosed cases of breast cancer in the United States and 470,000 in Europe each year.2

Topo I-inhibition is as an important DNA-damaging mechanism in the treatment of some cancers. However, the existing class of chemotherapy drugs known as Topo I inhibitors have had limited utility for patients because of their narrow therapeutic index. When dosed, these drugs reach high peak concentrations and diffuse quickly throughout the body — penetrating and damaging healthy tissue, such as bone marrow, as well as tumor tissue, which results in unwanted side effects. The rapid metabolism of these agents limits the ability of these drugs to act on tumor cells, potentially limiting their efficacy as well. These properties have limited their ability to be explored for the treatment of advanced breast cancer.

ONZEALD (etirinotecan pegol) is the first long-acting topoisomerase I-inhibitor (Topo I). ONZEALD is a new type of chemotherapeutic designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities.

Nektar Therapeutics invented ONZEALD using our unique chemistry platform and is developing it for the treatment of advanced breast cancer patients with a history of brain metastases.

In preclinical models, ONZEALD achieved a 300-fold increase in tumor concentration as compared to a first-generation topo I-inhibitor. 3 Because ONZEALD is a large molecule, it is believed to penetrate the leaky vasculature within the tumor environment more readily than normal vasculature, concentrating and trapping ONZEALD in the tumor tissue. ONZEALD has been evaluated in breast, ovarian, colorectal, brain and lung cancer.

Phase 3 Trials in Advanced Breast Cancer

Data from the first Phase 3 clinical trial of etirinotecan pegol in metastatic breast cancer, were published in the November 2015 issue of The Lancet Oncology (click here to view manuscript). This data was previously presented at the 2015 ASCO Annual meeting (click here to download this presentation).

A Phase 3 trial is ongoing in patients with metastatic breast cancer and brain metastases.


1 Witzel et al. Breast Cancer Research (2016) 18:8

2 American Cancer Society, Global Cancer Facts and Figures 3rd Edition, 2012.

3 Clin Cancer Res; (2012) 19(1); 268–78.

Future Oncology

2018 ESMO Congress

2018 ASCO Annual Meeting

San Antonio Breast Cancer Symposium, San Antonio, TX

2017 ASCO Annual Meeting

34th Annual Miami Breast Cancer Conference – March 9, 2017

2016 San Antonio Breast Cancer Symposium

6th Annual Brain Metastases Research and Emerging Therapy Conference

2015 ASCO Annual Meeting

SABCS 2014 Annual Meeting - December 8 - 11, 2014

26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics - November 18-21, 2014

2014 ASCO Annual Meeting - May 30 - June 3, 2014

American Association of Cancer Research (AACR) Annual Meeting 2014 - April 8 & 9, 2014

2014 Gastrointestinal Cancers Symposium - January 16-18, 2014