Background: Metastatic neuroendocrine tumors (NETs) have a poor prognosis and there are limited options after first-line treatment with somatostatin analogues (SSA)/chemotherapy. Therefore, new therapies are urgently needed. Survivin is an intracellular protein that alters cell division, function of cell death proteases and inhibits apoptosis. It is undetectable in adult cells and expressed in many tumors, making it an ideal target. SurVaxM is a 15 amino acid synthetic peptide vaccine. It stimulates antigen presentation via intracellular cell-surface target recognition and induces CD8+ & CD4+ T cells and IgG production. It was well tolerated in a phase I trial in recurrent glioma pts (Fenstermaker et al., Neurooncol; 2014). Prelim analysis from a phase II study in glioma patients (pts) showed its efficacy (Ahluwalia et al., Neurooncol; 2018). Targeting survivin in NETs is based on our work with tissue microarrays from gastroenteropancreatic (GEP) and lung NETs that showed that its expression correlated with a worse overall survival (Hanif et al., Oncotarget; 2020). We have an ongoing single-arm phase I trial evaluating the safety and immunogenicity of SurVaxM in metastatic NETs. Methods: Ten eligible pts with any grade metastatic GEP/lung origin NETs that are survivin positive by immunohistochemistry and have progression on SSA within the last 6 months on two CT scans >4 weeks apart per RECIST v1.1 are being enrolled. Pts receive a fixed dose of 500 mcg of SurVaxM in Montanide ISA 51 subcutaneously along with 100 mcg of GM-CSF q2 weeks X 4 doses. SSA is continued at the same dose as before. Pts free of progression and toxicity at 6 months get extra doses of SurVaxM q12 weeks, up to 1 year. Subjects are assessed continuously for safety per NCI CTCAEv5.0. Response assessment via CT scans per RECIST v1.1 q12 weeks. Primary objective is to assess safety of SurVaxM +/- SSA. Secondary objectives are to assess overall response rate, progression free survival, duration of response and vaccine immunological response (anti-survivin antibody titers and survivin-specific CD8 T-cell responses). Safety analysis is per Pocock stopping boundary with the assumption of true toxicity of 0.2 and unacceptable toxicity of 0.3 at a significance level of 0.05.To this date, eight patients were screened out of which five patients were enrolled. One patient did not meet the eligibility criterion due to negative survivin staining and the other two did not meet the RECIST v1.1 progression criterion. Of the five pts enrolled, two were of lung origin, two of GEP, and the remainder one of thymic origin. Three pts had high grade neuroendocrine carcinoma, one patient had atypical bronchial tumor and one with low-grade NET. Currently, two pts remain on the study. The enrollment is ongoing. The trial is funded by The Neuroendocrine Tumor Research Foundation.

The Neuroendocrine Tumor Research Foundation (NETRF).