On September 14, 2024 NuCana plc reported final data from the Phase 2 NuTide:701 study at the ESMO (Free ESMO Whitepaper) Congress on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor therapy (Press release, Nucana, SEP 14, 2024, View Source [SID1234646615]). In this cohort of 12 patients, most of whom had received at least two prior lines of PD-1 inhibitor therapy, nine (75%) achieved disease control, including two patients who achieved Partial Responses. One of these patients, who had received two prior lines of PD-1 inhibitor-based therapy and had progressed on their latest treatment of ipilimumab plus nivolumab within two months, achieved a 55% reduction in tumor volume. Seven of the 12 patients had a progression free survival time of greater than five months, which is highly atypical in this patient population. In addition to achieving these encouraging efficacy signals, the combination of NUC-7738 and pembrolizumab had a favorable safety profile.

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NUC-7738’s ability to sensitize PD-1 resistant tumors to rechallenge with PD-1 inhibitors is believed to be due to its ability to target multiple aspects of the tumor microenvironment (TME) via the disruption of RNA polyadenylation and subsequent changes to gene expression in cancer cells. In support of this hypothesis, data presented from tumor biopsies obtained before and after NUC-7738 based treatment demonstrated increases in genes related to antigen presentation and T-cell activation.

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We are very excited to share these data on NUC-7738 in combination with pembrolizumab in PD-1 inhibitor refractory and resistant patients with melanoma. Outcomes in this patient population are very poor, with median progression free survival of 2-3 months with the current standard of care, so we are very encouraged that the majority of patients who received this combination achieved a progression free survival of more than five months."

Mr. Griffith continued: "The translational data that has been generated in this study and in previous non-clinical studies give us confidence that the effects we are seeing are a result of NUC-7738 making previously resistant tumors sensitive to rechallenge with PD-1 inhibitors by targeting multiple aspects of the tumor microenvironment. Our data on NUC-7738 obtained in other tumor types indicate that this phenomenon is not restricted to melanoma and that NUC-7738 may have the ability to sensitize other PD-1 inhibitor resistant tumor types. We look forward to sharing our development plans for NUC-7738 in the near future."