Ariceum Therapeutics Advances 225Ac-SSO110 for Extensive Stage Small Cell Lung Cancer with Novel Radioligand Therapy Approach
核心洞察
Ariceum Therapeutics (搜索) presented data at EANM25 showcasing their SANTANA-225 Phase 1/2 clinical trial design for 225Ac-SSO110 (搜索), the first SSTR2 (搜索)-targeting antagonist labeled with Actinium-225 to undergo human trials in combination with checkpoint inhibitor therapy.
Preclinical studies demonstrate 225Ac-SSO110 (搜索) achieves superior tumor uptake and retention compared to 225Ac-DOTA-TATE (搜索), with complete tumor remissions after a single 30 kBq injection and 100% survival rates.
The global study will enroll approximately 20 patients in dose escalation for extensive stage small cell lung cancer (搜索) and Merkel cell carcinoma (搜索), with initial safety data expected in 2026 and preliminary efficacy results in 2027.
Ariceum Therapeutics (搜索) presented compelling data at the 38th Annual Congress of the European Association of Nuclear Medicine (EANM25) in Barcelona, showcasing their novel targeted alpha radioligand therapy 225Ac-SSO110 (搜索) for extensive stage small cell lung cancer (搜索) (ES-SCLC) and Merkel cell carcinoma (搜索) (MCC). The presentations highlighted both the innovative SANTANA-225 Phase 1/2 clinical trial design and preclinical data supporting the therapy's differentiated profile as a somatostatin receptor 2 (搜索) (SSTR2 (搜索)) positive malignancy treatment.
SANTANA-225 Clinical Trial Design
Dr. Elcin Zan from Cleveland Clinic presented the design of Ariceum's SANTANA-225 Phase 1/2 clinical trial (NCT06939036), which represents a first-in-class approach for patients with ES-SCLC and MCC. The global, open-label study will evaluate 225Ac-SSO110 (搜索) for first-line maintenance treatment of ES-SCLC or first-line MCC in patients receiving immune checkpoint inhibitor (CPI) therapy.
The clinical trial is expected to enroll approximately 20 patients in the dose escalation phase, followed by additional optional expansion cohorts of 15 patients per indication. The study will assess safety, tolerability, preliminary efficacy, and the recommended Phase 2 dose of 225Ac-SSO110 (搜索). Notably, 225Ac-SSO110 is the first SSTR2 (搜索)-targeting antagonist labeled with Actinium-225 to undergo human trials in combination with CPI therapy.
Superior Preclinical Performance
The second presentation demonstrated 225Ac-SSO110 (搜索)'s superior pharmacokinetic profile compared to 225Ac-DOTA-TATE (搜索) in preclinical studies. The company evaluated the biodistribution of Actinium-225 and its daughter radionuclides, including Bismuth-213, in an ES-SCLC xenograft model comparing the non-internalizing SSTR2 (搜索) antagonist SSO110 with the internalizing SSTR2 agonist DOTA-TATE.
The study results revealed that 225Ac-SSO110 (搜索)'s differentiated binding profile enables superior tumor uptake and retention compared with 225Ac-DOTA-TATE (搜索). Importantly, 225Ac-SSO110 exhibited similar retention of daughter radionuclides as the internalizing agonist while maintaining a more favorable therapeutic index. The short blood circulation half-life of 225Ac-SSO110 helps limit systemic redistribution of daughter radionuclides, reducing potential off-target exposure.
In prior studies, 225Ac-SSO110 (搜索) achieved complete tumor remissions after a single injection of 30 kBq, whereas 225Ac-DOTA-TATE (搜索) failed to control tumor growth with the same injected activity. Both treatments were well-tolerated with no histopathological abnormalities observed, and 225Ac-SSO110 demonstrated 100% survival in preclinical studies.
Clinical Development Timeline
"For the first time, we are presenting data showing minimal in-vivo redistribution of daughter radionuclides with 225Ac-SSO110 (搜索), a non-internalizing SSTR2 (搜索) antagonist, an important advance in our understanding of targeted alpha therapy," said Dr. Germo Gericke, Chief Medical Officer of Ariceum Therapeutics (搜索). "With the SANTANA-225 initial safety readout expected in 2026 and preliminary efficacy in 2027, we remain committed to setting new standards in both research and patient care for diseases with high unmet needs."
Addressing High Unmet Medical Need
The development of 225Ac-SSO110 (搜索) targets ES-SCLC and MCC, two diseases characterized by limited treatment options and poor prognosis. As the first maintenance radiotherapy approach for these conditions, 225Ac-SSO110 represents a potentially transformative treatment option for patients with aggressive and hard-to-treat cancers.
Bismuth-213 plays a critical role in therapeutic assessment as the longest half-life alpha-emitting daughter of Actinium-225, with its localization and retention within target tissue serving as key determinants of both safety and efficacy in targeted alpha therapies. The favorable daughter radionuclide retention profile of 225Ac-SSO110 (搜索) positions it as a next-generation alpha-emitting radioligand therapy for SSTR2 (搜索)-positive tumors.