Onzeald™ (etirinotecan pegol)
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).
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.
- Phase 3 Study of Etirinotecan Pegol versus Treatment of Physician’s Choice in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases Previously Treated With an Anthracycline, a Taxane, and Capecitabine
- Etirinotecan Pegol: Survival Advantage Over Standard of Care Drugs in a Model of Brain Metastases of Breast Cancer
- ATTAIN: Phase 3 Study of Etirinotecan Pegol (EP) versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer and Brain Metastases (BCBM)
- Phase III trial of etirinotecan pegol (EP) versus Treatment of Physician's Choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C): The BEACON study.
- Etirinotecan Pegol Target-Specific Pharmacodynamic Biomarkers in Circulating Tumor Cells from Patients with Metastatic Breast Cancer in the Phase 3 BEACON Study
- Combining the long-acting topoisomerase 1 inhibitor etirinotecan pegol with the PARP inhibitor rucaparib to provide anti-tumor synergy without increased toxicity
- Etirinotecan Pegol in the Treatment of High-Grade Glioma: A Phase 2 Trial
- Etirinotecan Pegol Accumulates in Breast Cancer Brain Metastases and Prolongs Survival in an Experimental Model of Brain Metastases of Human Triple Negative Breast Cancer
- A Phase 1 Study of Etirinotecan Pegol (NKTR-102) in Combination with 5-Flourouracil/Leucovorin
- View all Etirinotecan pegol (NKTR-102) scientific and clinical data publications