Neuroendocrine tumors arise from neuroendocrine cells and are defined as a rare disease; with 5-6 new cases per 100,000 individuals diagnosed each year.1
Healthy neuroendocrine cells are part of both the endocrine and the nervous system and can be found throughout the body, releasing neurotransmitters, cell messengers or hormones into the blood. Somatostatin receptors can be found on the surface of these cells. Tumor cells of neuroendocrine origin often express an increased number of these somatostatin receptors, showing a unique tumor characteristic that differs from that of healthy neuroendocrine cells.2
75 % of all neuroendocrine tumors are of gastroenteric or pancreatic origin.3 They are called gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and are found in the digestive system or related parts of the body. GEP-NETs are often asymptomatic and challenging to diagnose. This is why they are often diagnosed at a late stage with metastases and limited possibility of surgery.
N.c.a. 177Lu-Edotreotide is known as an innovative Targeted Radionuclide Therapy agent and is under investigation in the phase III clinical trial COMPETE. N.c.a. 177Lu-Edotreotide shows a favorable safety profile and promising efficacy for the treatment of GEP-NETs, for which only a few suitable and well-tolerated therapies are marketed.
N.c.a. 177Lu-Edotreotide consists of two molecular components – firstly, Edotreotide (DOTATOC), an octreotide-derived somatostatin analog, and secondly, EndolucinBeta® (no-carrier-added (n.c.a.) Lutetium-177 chloride) a synthetic, low-energy beta-emitting therapeutic radioisotope.
The targeting molecule Edotreotide contains DOTA, which functions as a chelator for radioisotopes, and TOC, a synthetic somatostatin receptor ligand. It binds with high affinity to somatostatin receptors (subtypes 2 and 5) and retains both its receptor-binding properties and its physiological function when labeled with 177Lu. Upon binding to Somatostatin receptors in vivo, n.c.a. 177Lu-Edotreotide is internalized and retained by tumor cells. Upon decay, the isotope emits cytotoxic medium-energy beta particles of ≤ 1.7 mm path length in soft tissue.
N.c.a. 177Lu-Edotreotide received an orphan designation as a treatment for GEP-NETs based on the data from a phase II clinical study, which demonstrated a significant benefit (substantially improved progression-free survival, PFS). Furthermore, a uniquely low uptake by normal organs and a high tumor-to-kidney ratio were shown.4
In 2017, the phase III clinical trial COMPETE with n.c.a. 177Lu-Edotreotide as the Investigational Medicinal Product (IMP) started. COMPETE is an international, prospective, randomized, controlled, open-label, multicenter phase III clinical trial to evaluate the efficacy and safety of Targeted Radionuclide Therapy with n.c.a. 177Lu-Edotreotide compared to the standard therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+) GEP-NETs.
1 Bryan Oronsky et al., 2017, Neoplasia Vol. 19, pp. 991-1002
2 Papotti et al., 2002, Virchows Archiv 440(5): 461-75
3 Pape et al., 2000, Der Onkologe 6: 624–633
4 Baum et al., 2016, Theranostics 6(4): 501–510
* n.c.a. 177Lu-Edotreotide is not authorized for marketing in any country at the time.
* Please also see study information on www.clinicaltrials.gov