ITM Isotope Technologies Munich (ITM), announced on Nov. 13 that the U.S. FDA has accepted the company’s NDA for n.c.a. 177Lu-edotreotide (ITM-11, 177Lu-edotreotide), a targeted radiotherapeutic investigational agent for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Edotreotide is a synthetic form of somatostatin hormone and binds with high affinity to somatostatin receptors (SSTRs) expressed on tumor cells, targeting GEP-NET tumors.
PDUFA date for the NDA is set for August 28, 2026.
The phase III COMPETE trial for ITM-11 showed a longer Progression Free Survival (PFS), higher overall response rate (ORR), and a favorable safety profile .
- PFS, primary end point: Patients on ITM-11 had a significantly longer median PFS compared to those on Everolimus (brand name Afinitor), the comparator standard, of 23.9 vs. 14.1 months. Everolimus is a macrocyclic lactone derivative of rapamycin that acts as a targeted therapy by inhibiting the mammalian target of rapamycin (mTOR) pathway. It is a primary standard of care for certain neuroendocrine tumors because the mTOR pathway is frequently overactive in these cancers, and clinical trials have demonstrated that everolimus significantly slows tumor growth and disease progression (Ref. https://pubchem.ncbi.nlm.nih.gov/compound/Everolimus)
- ORR, secondary endpoint: The trial met the secondary endpoint, showing significantly higher ORR for ITM-11 (21.9%) compared to everolimus (4.2%).
- Safety and Tolerability was satisfactory.
- Overall Survival (OS): While data is still awaited, preliminary results indicate a trend towards longer median overall survival in the ITM-11 group.
- Dosing Interval: ITM-11 was tested with a 12-week dosing interval.
Analysis
Lutathera binds to SSTRs, similar to ITM-11, but binding peptide is structurally different.
Lutathera uses Lu-177 vs. n.c.a. Lu-177 in ITM-11, a higher-purity form of the isotope. N.c.a. Lu-177 has none or negligible amount of the long-lived radioactive impurity Lutetium-177m associated with non- n. c. a. Lu-177. This translates to less long-term radiation exposure concerns to patients and simpler waste disposal process for manufacturing and hospitals.
The 12 week dosing regimen of ITM-11 offers improved convenience and logistics compared to Lutathera’s 8-week schedule.
Lutathera’s NETTER-1 phase III trial used comparator Octreotide LAR (Octreotide Long-Acting Release), a synthetic version of the natural somatostatin hormone. NETTER-1 trial recorded PFS of 25 months based on post-hoc analysis, similar to ITM-11.
