Novartis’ Lutathera Clears Phase III as Frontline Treatment for Rare Neuroendocrine Cancer

Novartis building_iStock, JHVEPhoto

Pictured: Novartis logo on its office in California/iStock, JHVEPhoto 

Novartis’ radioligand therapy Lutathera (lutetium Lu 177 dotatate) met its primary endpoint in the Phase III NETTER-2 trial in gastroenteropancreatic neuroendocrine tumors, the company announced Monday.

NETTER-2 is a randomized and open-label trial that evaluated Lutathera as a first-line option in 222 patients with grade 2 or 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Only those whose cancers were positive for the somatostatin receptor (SSTR) were eligible for enrolment into NETTER-2.

When used in combination with high-dose long-acting octreotide, Lutathera led to a significant improvement in progression-free survival (PFS)—the study’s primary endpoint—compared with octreotide alone. In terms of safety, NETTER-2 did not find any new signals of concern and Lutathera’s adverse event profile in the study was consistent with what had been previously established.

Novartis did not provide specific efficacy and safety figures, though it promised to do so at a future medical congress. The company also said in Monday’s announcement that it would discuss NETTER-2’s results with regulatory authorities.

Jeff Lagos, Novartis executive vice president and global head of oncology development, in a statement called NETTER-2’s outcomes “quite remarkable” and said that these underline Lutathera’s potential to make a “meaningful impact” in patients with newly diagnosed advanced GEP-NETs.

NETs are a type of malignancy that originate from neuroendocrine cells found throughout the body. While most NETs are typically slow-glowing, some subtypes tend to progress rapidly and often go undiagnosed until they have reached advanced stages. These cancers are also usually associated with worse prognoses.

Lutathera is a peptide receptor radionuclide that selectively targets and binds to SSTRs found on the surface of cancer cells. Once bound to the SSTR, Lutathera is designed to enter the cells and deliver its radiation specifically to target sites. The radiotherapeutic agent won the FDA’s approval in January 2018 for patients with GEP-NETs who progress despite standard treatment.

The 2018 regulatory victory was based on the Phase III NETTER-1, which established Lutathera’s superiority over standard of care in patients with inoperable midgut NETs. With NETTER-2, Novartis hopes to push Lutathera into the front-line setting in this indication.

Monday’s data drop comes as Novartis appears to be trimming its oncology business. Last week, the company returned the investigational monoclonal antibody tislelizumab to BeiGene after the candidate had run into regulatory delays. Tislelizumab is an anti-PD-1 candidate and was being proposed as a treatment for esophageal squamous cell carcinoma.

The European Commission has already approved the therapeutic antibody for this indication. Tislelizumab is also authorized across 11 indications in China.

In August 2023, Novartis also dropped the development of the anti-TGFβ antibody NIS793, which it returned to Xoma Corporation. NIS793 was being assessed in a Phase III study in pancreatic ductal adenocarcinoma as a first-line combination treatment with gemcitabine and nab-paclitaxel.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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