ITM-11 for Neuroendocrine Tumors (GEP-NETs)

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.

ITM-11 (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. ITM-11 indicates a good safety profile and potentially promising efficacy for the treatment of GEP-NETs, for which only a few suitable and well-tolerated therapies are marketed.

ITM-11 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, ITM-11 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.

ITM-11 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

ITM-11 is currently being evaluated in ITM’s two phase III clinical trials, COMPETE and COMPOSE. While COMPETE (NCT03049189) is evaluating ITM-11 for the treatment of patients with grade 1 and grade 2 GEP-NETs, the radiopharmaceutical candidate is also being investigated in COMPOSE (NCT04919226), for patients with well-differentiated high grade 2 and grade 3 GEP-NETs.

Additional clinical programs with ¹⁷⁷Lu-edotreotide include KinLET, a Phase 1 pediatric trial in SSTR-positive tumors (NCT0644133) and LEVEL, a Phase 3 investigator-sponsored trial in lung and thymus neuroendocrine tumors (NCT05918302).

¹ Bryan Oronsky et al., 2017, Neoplasia Vol. 19, pp. 991-1002 Review paper
² Papotti et al., 2002, Virchows Archiv 440(5): 461-75 electronic publication
³ Pape et al., 2000, Der Onkologe 6: 624–633 overview article
⁴ Baum et al., 2016, Theranostics 6(4): 501–510 Phase 2 study
 

Please note: ITM-11 (n.c.a. ¹⁷⁷Lu-edotreotide) is not authorized for marketing in any country at this time.
Please also see study information on www.clinicaltrials.gov