On April 8, 2022 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biotechnology company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported 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 (Press release, Checkmate Pharmaceuticals, APR 8, 2022, View Source [SID1234611724]). 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.

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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) (Abstract #: LB107: NCT03084640 and NCT03438318)

During the 2022 AACR (Free AACR Whitepaper) Late-Breaking Research: Clinical Research 2 Poster Session on Tuesday, April 12 from 9:00am – 12:30pm CT, 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
"These data suggest that the tumor regression we have seen in patients treated with intratumoral vidutolimod with or without checkpoint inhibitors may be predicted from the presence of one or more novel transcriptional signatures in the baseline tumor biopsies," said Dr. Art Krieg, Founder and Chief Scientific Officer of Checkmate. "These signatures are consistent with what we know about TLR9 biology and they provide clues to possible new combinations and patient populations who may be especially amenable to vidutolimod treatment. We look forward to determining the prevalence of these signatures in other cancers and to exploring the potential for a biomarker-based enrichment strategy across cancer."