161Tb-DOTA-LM3 / Paul Scherrer Institute, University Hospital Basel - LARVOL DELTA

Interim results of the BETA Plus Phase 0b Study: Targeted beta -plus conversion - and auger electron therapy with terbium -161 labeled somatostatin receptor antagonist DOTA -LM3 (ENETS 2026) - P1 | "BACKGROUND: Radioligand therapy with lutetium-177 labeled so - matostatin receptor agonists (177Lu-DOTATATE or 177Lu-DO - TATOC) showed limited response rate and durability. Increasing the peptide mass from <100 µg to 300- 400 µg reduced the absorbed doses to the tumor, and to a similar extent also to bone marrow and kidneys, resulting in no improve - ment of the therapeutic index. An increase in peptide mass may protect the bone marrow. Overall, there is no safety concern with escalated activity and peptide mass of 161Tb-DOTA-LM3."

Gastrointestinal Neuroendocrine Tumor • Hematological Disorders • Hematological Malignancies • Neuroendocrine Tumor • Renal Cell Carcinoma • Solid Tumor • Thrombocytopenia • SSTR

Targeted β--Particle Plus Conversion and Auger-Electron Therapy with 161Tb-Labeled Somatostatin Receptor Antagonist DOTA-LM3: A Phase 0 Study. (PubMed, J Nucl Med) - "The tumor-to-bone marrow absorbed dose ratio was in the same range for [161Tb]Tb-DOTA-LM3 as for [177Lu]Lu-DOTATOC. The administration of 1 GBq of [161Tb]Tb-DOTA-LM3 was safe for all patients, without relevant adverse events."

Journal • Gastrointestinal Neuroendocrine Tumor • Hematological Malignancies • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Targeted beta- plus auger and conversion electron therapy with terbium-161 labelled somatostatin receptor antagonist DOTA-LM3 – BETA plus phase 0 study (ENETS 2025) - P1 | "INTRODUCTION Radioligand therapy with lutetium-177 labelled somatostatin receptor (SSTR) agonists (177Lu-DOTATATE or 177Lu-DOTATOC) showed limited response rate and durability. CONCLUSION 161Tb-DOTA-LM3 delivered a 7.6-fold higher tumour absorbed dose compared to 177Lu-DOTATOC, with a 1.2-fold lower tumour-to-bone marrow dose ratio. The administration of 1 GBq 161Tb-DOTA-LM3 was safe."

Anemia • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Leukopenia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • Thrombocytopenia • SSTR

[PREPRINT] Comparison of the tolerability of 161Tb- and 177Lu-labeled somatostatin analogues in the preclinical setting (bioRxiv) - "The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161Tb- and 177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p<0.05) while changes were less pronounced in mice injected with the SSTR agonist."

Preclinical • Preprint • Oncology • Solid Tumor

Beta plus: Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3) (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2022 ➔ Apr 2023

Enrollment open • Trial initiation date • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor