Checkmate Pharmaceuticals, Inc. announced the presentation of biomarker signature data from two studies evaluating vidutolimod, a first-in-class, immunostimulatory, noninfectious virus-like particle (VLP) containing a CpG-A Toll-like receptor 9 (TLR9) agonist. The first study evaluated vidutolimod in patients with advanced anti-PD-(L)1 refractory melanoma who received intratumoral vidutolimod monotherapy or in combination with intravenous pembrolizumab, and the second evaluated patients with anti-PD-(L)1 refractory non-small cell lung cancer (NSCLC) who received vidutolimod and atezolizumab. The objective of these analyses was to identify transcriptional signatures specific to the antitumor activity of treatment with vidutolimod monotherapy or in combination with PD-1 blockade in these two subsets.

Novel transcriptional signatures associated with antitumor activity in vidutolimod (vidu)-treated patients (pts) with anti-PD-1-refractory melanoma and non-small cell lung cancer (NSCLC). During the 2022 AACR Late-Breaking Research: Clinical Research 2 Poster Session on April 12, Art Krieg, M.D., Founder and Chief Scientific Officer of Checkmate, presents analyses of RNA Seq data from baseline biopsies of tumors in patients with anti-PD-1-refractory melanoma and NSCLC. Key highlights from these clinical trial biomarker data include: Expression of a 35-gene COPII/Golgi core signature was associated with antitumor activity of intratumoral vidutolimod ± intravenous anti–PD-(L)1. This finding is consistent with published reports that COPII vesicle and Golgi trafficking are critical for TLR9 trafficking and function; Association with response to vidutolimod monotherapy suggests that the COPII/Golgi core signature is linked to effective TLR9 agonism.

The signature was independent of tumor inflammation and baseline patient characteristics such as LDH, presence of liver metastases, or tumor burden; Machine learning of the RNA Seq dataset revealed that the COPII/Golgi signature in combination with ELF2 expression provided a stronger differentiation between responders and non-responders to vidutolimod, regardless of baseline tumor inflammation; A macrophage signature was associated with nonresponse in T cell–inflamed melanoma, consistent with other evidence that high concentrations of tumor-associated macrophages (or myeloid-derived suppressor cells) may suppress TLR9 activation by vidutolimod; The presence of these signatures and potential association with clinical response is being evaluated in further RNA Seq datasets being generated from ongoing clinical trials of vidutolimod in combination with various checkpoint inhibitors.