Targeted radiopharmaceutical therapies have emerged as an excellent treatment option for patients with inoperable metastatic neuroendocrine tumors (NETs). Currently approved therapies work by targeting somatostatin receptor expressed on NET cells. These therapies are expected to minimize the damage to healthy tissues while effectively treating tumors cells. With the commercial success of Lutathera ( Lu177 based, a β emitter, Novartis), this field continues to offer new hope for improved outcomes in the NET care. Following is the summary of a few pipeline radiopharmaceutical candidates for NETs.
- ITM-11 (177Lu-edotreotide) – ITM Isotope Technologies: Most advanced somatostatin binding ITM candidate in phase III clinical trials, COMPETE, for the treatment of patients with grade 1 and grade 2 GEP-NETs.
- AlphaMedix™ (212Pb-DOTAMTATE) – RadioMedix / Orano Med / Sanofi
212Pb-DOTAMTATE is being developed for GEP-NETs with FDA Breakthrough Therapy Designation for a first alpha emitting candidate. Currently in Phase II trials, it offers a potentially more powerful treatment option for patients who have not received peptide receptor radionuclide therapy (PRRT). - VMT-α-NET – Perspective Therapeutics
A Pb212 based alpha-emitting radiopharmaceutical targeting somatostatin receptor 2-positive NETs and other SSTR2 expressing tumors, VMT-α-NET is in stage 1/2 clinical trials. Incorporation of Pb203 leads to a gamma ray generating PET radiotracer illustrating theranostic properties of this drug candidate. - RayzeBio (Bristol Myers Squibb candidate)
Following its acquisition by BMS, RayzeBio is advancing a novel radiopharmaceutical candidate RYZ101 in phase 3 clinical for GEP-NETs expressing SSTR2 biomarker with patients refractory to Lu177 SSA treatment. It uses Ac225 as the therapeutic radioisotope.
A regulatory filing of the generic version of Lutathera has also been submitted. Lantheus Medical Imaging has submitted Abbreviated New Drug Application (ANDA) for PNT2003, the drug candidate Lantheus acquired from Point Biopharma, which is now a part of Eli Lilly company. Novartis, the manufacturer of Lutathera, has challenged the application.
