Project Funding Details

The incidence of neuroendocrine tumors (NETs) is continuously rising and the therapeutic options for patients with metastatic disease are limited. Successful theranostics targeting the somatostatin receptor type 2 (SSTR2) with diagnostic and therapeutic receptor agonists are the standard of care in Europe and other countries, and have already been integrated into clinical guidelines in Europe (1). The recent NETTER-1 trial clearly demonstrated that 177Lu-DOTATATE (Lutathera™) therapy in addition to 30 mg cold octreotide given to appropriately selected SSTR2-positive patients with metastatic midgut NETs results in markedly improved progression-free survival and significantly higher response rates than high-dose octreotide (60 mg) (2). Despite the clear progression free survival (PFS) benefit of patients undergoing SSTR2-directed Peptide Receptor Radio-Nuclide Therapy (PRRNT), patients experience relapse. The recent introduction of monoclonal antibodies for cancer immunotherapy resulted in significant improvement of tumor response in numerous tumor entities including melanoma, lung cancer and some hematological cancers (3). Combination of immunotherapy with ionizing radiation appears to be promising (4–6). Therefore we hypothesized that combination of PRRNT and immunotherapy increases anti-tumorigenic effects and prolongs survival. We propose here a preclinical evaluation of SSTR2-targeted PRRNT with 177Lu-DOTATATE in addition to immunotherapy (anti-PD1) to generate synergism in a murine model of SSTR2-expressing tumors (4,7–9). This preclinical evaluation will provide important information whether a translation into the clinic is warranted.