A novel nonpeptide drug conjugate (NDC) for the treatment of somatostatin receptor 2-expressing tumours

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Introduction: Somatostatin receptor 2 (SST2) is an established target for the treatment of NETs and potentially other solid tumours.

Aim(s): CRN09682 is a non-radioactive, nonpeptide drug conjugate (NDC) optimised for delivery of a cytotoxic payload to SST2-expressing tumours.

Materials and methods: CRN09682 was developed by linking a small-molecule, nonpeptide SST2 agonist with monomethyl auristatin E (MMAE) via a spacer and a cleavable linker. CRN09682-SST2 complex formation were evaluated using both cAMP and receptor internalisation assays. SST2-expressing small cell lung cancer (SCLC) cell lines NCI-H524 and NCI-H69 and SST2 receptor null cells H460 were treated with CRN09682. Intratumoural concentrations of CRN09682 and MMAE were determined in NCI-H524 xenografts (CDX). Anti-tumour activity of CRN09682 was characterised in NCI-H524 and NCI-H69 CDX and PDX models.

Conference:

Presenting Author:

Authors: Zhao J, Sturchler E, Yang B, Chen M, Tang Y,

Keywords: somatostatin, solid tumour, drug conjugate, internalisation, cytotoxicity,