212Pb-AR-RMX

A radiopharmaceutical from ITM Isotope Technologies Munich reduced the risk of disease progression or death by 33% versus Novartis' targeted molecular therapy Afinitor (everolimus) in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The outcome of the Phase III COMPETE study was first top-lined in January, with the announcement marking one of only a handful of wins for a radiopharmaceutical in a head-to-head trial. Detailed results were presented Thursday at the European Neuroendocrine Tumor Society (ENETS) annual meeting.The trial compared ITM-11 (177Lu-edotreotide) with Afinitor in 309 patients with inoperable, progressive Grade 1 or 2 somatostatin receptor (SSTR)-positive GEP-NETs. According to ITM, approximately 15% of people in each trial arm were treatment naïve, with the remaining 85% or so having received one prior therapy.Results showed that median progression-free survival (PFS) for ITM's therapeutic was 23.9 months, which was significantly and clinically better than the 14.1 months for Afinitor. In comparison, in the Phase III NETTER-2 trial, Novartis' peptide receptor radionuclide therapy Lutathera (lutetium Lu 177 dotatate) reduced the risk of disease progression or death by 72% as a first-line therapy for patients with SSTR-positive well-differentiated Grade 2/3 advanced GEP-NETs versus high-dose octreotide LAR alone, with median PFS in the two arms of 22.8 months and 8.5 months, respectively.ITM told FirstWord that the choice of Afinitor as a comparator in COMPETE was "backed by scientific evidence of efficacy and high clinical acceptance after market authorisation." The company suggested that this decision set "a higher standard for meeting the primary endpoint in more advanced grade tumours," adding that it hopes "physicians will recognise the higher threshold of our study design."FDA filing this year"These successful results validate our decision to design a pivotal Phase III trial directly comparing a targeted radiopharmaceutical against a targeted molecular therapy," CEO Andrew Carey said. Based on the findings, ITM plans to seek approval of ITM-11 in the US this year; however, the company told FirstWord that it is "currently prohibited" from filing in Europe until 2029 due to orphan drug designation on Lutathera.Top-line results also showed that interim median overall survival (OS) was 63.4 months for ITM-11. That was numerically higher than the 58.7 months seen with Afinitor, but not statistically significant at the current analysis. ITM noted that patients were allowed to start an alternative therapy after disease progression, "potentially confounding" the OS data."These data show unequivocal support for [ITM-11's] potential benefit in extending PFS," remarked study investigator Jaume Capdevila, adding that the radiopharmaceutical's "convenient dosing schedule and favourable safety results reinforce its potential as a compelling new treatment option."In COMPETE, patients were treated with ITM-11 every three months for up to four cycles, or with Afinitor daily for up to 30 months, or until disease progression. Meanwhile, ITM's therapy was well tolerated, with treatment-emergent adverse events occurring at a rate of 82.5%, compared with 97% for Afinitor. However, there was one Grade 2 event of myelodysplastic syndrome in the ITM-11 arm.Growing optionsNeuroendocrine tumours are one of the few cancers that have so far benefited from the approval of radiopharmaceuticals. Novartis currently markets Lutathera as a treatment for SSTR-positive GEP-NETs, while Sanofi also has skin in the game, having reached a deal last year to join forces with RadioMedix and Orano Med on the radioligand medicine AlphaMedix (212Pb-DOTAMTATE).Something that differentiates ITM from other players, however, is that it has worked in the radiopharma space for over 20 years and has manufacturing in-house. "Together, with our global isotopes manufacturing business, robust supply chain and experienced clinical and commercial team, we believe we are uniquely positioned as a standout leader in the fast-growing radiopharmaceutical industry," Carey said.ITM-11 — which combines the therapeutic β-emitting radioisotope lutetium-177 with the synthetic SSTR agonist edotreotide — is also being investigated in the Phase III COMPOSE trial in patients with well-differentiated, aggressive Grade 2 or 3 SSTR-positive GEP-NETs.

ITM-11 combines beta-emitting radioisotope lutetium-177 with somatostatin receptor (SSTR) agonist edotreotide. Credit: Love Employee via Getty Images. ITM Isotope Technologies Munich SE is gearing up to enter the US market with its radiopharmaceutical therapy, ITM-11 (177Lu-edotreotide), after promising Phase III trial results showed a significant advantage over Novartis’s targeted therapy Afinitor (everolimus) in treating gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The company plans to seek regulatory approval later in 2025 following data from the Phase III COMPETE trial (NCT03049189). The full results were presented at the European Neuroendocrine Tumor Society (ENETS) annual meeting on 6 March in Krakow, Poland. An initial topline announcement on the trial meeting its primary endpoint was made in January 2025. The COMPETE trial evaluated ITM-11 in direct comparison with Afinitor in 309 patients with inoperable, progressive Grade 1 or 2 somatostatin receptor (SSTR)-positive GEP-NETs. Patients treated with ITM-11 had a median PFS of 23.9 months, compared to 14.1 months for Afinitor. While the interim median overall survival (OS) was numerically higher for ITM-11 at 63.4 months versus 58.7 months for Afinitor, the difference was not statistically significant, with ITM noting that OS data may have been affected by patients switching to alternative therapies after disease progression. The German company also reported new safety data. In the ITM-11 group, 82.5% of patients experienced treatment-emergent adverse events (TEAEs) compared to 97% of patients taking Afinitor. Radiopharmaceuticals have gained traction in oncology, particularly for neuroendocrine tumours. Novartis currently markets Lutathera (lutetium Lu 177 dotatate), an approved peptide receptor radionuclide therapy (PRRT) for SSTR-positive GEP-NETs. Sanofi has also entered the space, having partnered with RadioMedix and Qrane Med to develop AlRhaMedix (212Pb-DOTAMTATE), a radioligand therapy for neuroendocrine tumours. If approved, ITM-11 would compete with Lutathera. Novartis reported Lutathera sales of $724m in 2024, with forecasts projecting revenue growth to $910m by 2030, according to GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology. The rising interest in radiopharmaceuticals has led to increased investment from major pharmaceutical companies. Sanofi signed a $100m licensing agreement with RadioMedix and Qrane Med in September 2024, following Eli Lilly’s $1.1bn deal with Aktis Oncology in May 2024. AstraZeneca also expanded its radiopharmaceutical portfolio with a $2bn acquisition of Fusion Pharmaceuticals in June 2024. Despite growing demand, radiopharmaceutical supply chains have faced challenges. There have been shortages of the isotope actinium-225, used in the development of radiopharmaceuticals for treating metastatic castration-resistant prostate cancer (mCRPC), as companies like Novartis, Eli Lilly, and Johnson & Johnson pursue candidates utilising the isotope. ITM differentiates itself in the competitive landscape by maintaining in-house manufacturing capabilities. “Together, with our global isotopes manufacturing business, robust supply chain, and experienced clinical and commercial team, we believe we are uniquely positioned as a standout leader in the fast-growing radiopharmaceutical industry,” stated ITM’s CEO Andrew Cavey. In the announcement accompanying the data, Cavey said that the company plans to initiate another pivotal Phase III trial to further compare radiopharmaceuticals with targeted molecular therapies in Grade 1/2 GEP-NETs. “With this successful readout, 177Lu-edotreotide becomes the first drug candidate in ITM’s broad portfolio of early-to late-stage radiopharmaceuticals to deliver positive Phase III results and progress towards NDA submission and commercial launch preparations,” added Cavey.