On October 26, 2022 NuCana plc (NASDAQ: NCNA) reported that non-clinical data from two poster presentations at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Annual Meeting being held from October 26 to 28, 2022 (Press release, Nucana BioPharmaceuticals, OCT 26, 2022, View Source [SID1234622403]).
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Abstract 185: NUC-3373 is a potent TS inhibitor and induces DNA damage in NSCLC cancer cells regardless of histological subtype
Pemetrexed is an important therapeutic option for first-and second-line adenocarcinoma lung cancers, but is not recommended in squamous lung cancer due to higher levels of thymidylate synthase (TS) expression. NUC-3373 was shown to be a more potent inhibitor of TS than both pemetrexed and 5-FU. NUC-3373 generated high intracellular levels of the anti-cancer metabolite FUDR-MP, resulting in TS inhibition, and the DNA-targeting metabolite, FUDR-TP. This resulted in extensive DNA damage in both adenocarcinoma and squamous carcinoma cell lines. These data highlight that NUC-3373 may be an effective treatment for non-small cell lung cancer (NSCLC) regardless of histological subtype and basal TS expression.
Abstract 128: NUC-3373 induces DAMPs from NSCLC cells potentiating a favorable immunogenic microenvironment
NUC-3373 causes NSCLC cells to release damage associated molecular patterns (DAMPs), molecular signals that activate immune cells leading to immunogenic cell death (ICD). NUC-3373 also enhanced the cell surface expression of the transmembrane protein PD-L1 in lung cancer cell lines, highlighting a potential role for NUC-3373 to enhance immunotherapy efficacy. The addition of pembrolizumab, an anti-PD-1 antibody, to NUC-3373 in a co-culture system where NSCLC cells were incubated alongside human-derived immune cells also enhanced ICD, highlighting a potential role for NUC-3373 as an attractive combination partner for immune checkpoint inhibitors in NSCLC.
Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer, said: "These data are highly supportive of our strategy to combine NUC-3373 with pembrolizumab and to investigate NUC-3373 in patients with NSCLC. We have initiated the NuTide:303 study evaluating NUC-3373 in combination with either pembrolizumab in patients with advanced solid tumors or in combination with docetaxel in patients with non-small cell lung cancer. We have also initiated a randomized study in second-line CRC patients comparing NUFIRI plus bevacizumab to FOLFIRI plus bevacizumab, the global standard of care, and we look forward to sharing data from both of these studies in 2023."