ITM hopes to Compete against Lutathera

Novartis’s radiotherapeutic Lutathera sold over $700m in 2024, and Germany’s ITM wants a piece of this action, reporting competitive-looking data on Thursday from a phase 3 trial of its rival asset, ITM-11, in second-line gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

While the Compete study met its primary endpoint of progression-free survival, however, it fell short on the key secondary outcome of overall survival, with ITM noting that this could have been confounded by patient crossover. Lutathera’s Netter-1 study, in a similar setting, also flunked on OS, but this didn’t stop that asset getting approved in 2018.

The Compete data were presented at the European Neuroendocrine Tumor Society (ENETS) conference in Krakow, Poland.

Cross-trial comparison of ITM-11 vs Lutathera

Notes: *final analysis, Jan 2021; **OS endpoint not met.

When asked by ApexOnco, privately held ITM declined to disclose how many patients in Compete had crossed over and to which therapies, saying it was still analysing the data.

A spokesperson noted that on progression patients in the everolimus control arm were permitted to receive ITM-11, but added that progressing patients could also cross over to other therapies, “including radiopharmaceutical therapy and chemotherapy”.

This crossover conundrum looks similar to that seen with another Novartis radiopharmaceutical, Pluvicto, in the PSMAfore trial, which the Swiss company has delayed filing by around a year.

When asked if ITM-11 could suffer the same fate, ITM replied: “It’s an important question to ask, and at this time it’s premature for us to anticipate what the FDA will want.” The company plans to file a new drug application this year.

Similarities and differences

Lutathera and ITM-11 both target somatostatin receptor 2 (SSTR2) and both use lutetium-177 as the radioisotope, and both Compete and Netter-1 enrolled patients with SSTR2-positive NETs.

But there are some notable differences between the trials. For one, Compete focused on NETs of gastroenteric or pancreatic origin, while Netter-1 enrolled those with midgut NETs. And Compete enrolled first and second-line patients, while Netter-1 included patients who’d progressed on the somatostatin analogue Sandostatin. 

While Netter-1 tested Lutathera plus Sandostatin versus Sandostatin alone, Compete evaluated ITM-11 monotherapy – something ITM cited as a potential advantage with its project.

In Compete the control arm was everolimus, an established second-line option. When asked why the study didn’t test ITM-11 head-to-head against Lutathera, ITM replied that the Novartis drug wasn’t approved when it started the trial, in 2017.

As for safety in Compete, there were fewer treatment-related adverse events with ITM-11 versus everolimus, at 83% and 97% respectively. However, there was one serious (grade 2) treatment-emergent adverse event of myelodysplastic syndrome deemed related to ITM-11.

Novartis is trying to move Lutathera into the front-line setting, helped by the Netter-2 and, more recently, Netter-3 studies. ITM is also carrying out the Compose trial, in first and second-line grade 2-3 GEP-NETs, which is set to complete in 2027.