On October 18, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported data at the European Society for Medical Oncology Congress 2025 ("ESMO") on a new model system investigating the synergistic effects of NUC-7738 and PD-1 inhibition in primary organoids derived from patients with renal cell carcinoma ("RCC").

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Using patient-derived organoids ("PDOs") from ten patients with RCC and autologous tumor-infiltrating lymphocytes ("TILs"), co-culture experiments reveal that NUC-7738 enhances the effectiveness of PD-1 inhibitors, resulting in increased tumor cell killing. This combinatorial approach may offer a new option for cancers that no longer respond to anti-PD-1 therapy by targeting multiple aspects of the tumor microenvironment through the disruption of RNA polyadenylation and subsequent changes in cancer cell gene expression.

The data presented at ESMO (Free ESMO Whitepaper) reinforces the mechanism of action for NUC-7738 as observed in the ongoing Phase 1/2 NuTide:701 clinical study. Data to date from NuTide:701 have demonstrated a favorable safety profile, meaningful tumor volume reduction, and prolonged progression-free survival in patients with PD-1 inhibitor refractory and resistant metastatic melanoma.

Andrew Kay, NuCana’s Executive Chairman said: "We are excited to share these new data on NUC-7738 in combination with PD-1 inhibitors in a real-time organoid model system. In addition to demonstrating clear benefits of combining PD-1 inhibitors with NUC-7738, similar to those seen in patients on the ongoing NuTide:701 study, this may lead to robust, patient-specific testing for a selection of immune checkpoint therapies."

Mr. Kay continued: "The translational data that has been generated in this study increases our confidence that the effects we are seeing are a result of NUC-7738 targeting multiple aspects of the tumor microenvironment and increasing PD-1 inhibition. Our data on mechanism of action of NUC-7738 indicate that the phenomena are not restricted to a single tumor type, and that NUC-7738 may have the ability to sensitize many cancers to PD-1 inhibitor therapy."

Based on the exciting initial data from the Phase 1/2 NuTide:701 clinical study, regulators have approved the expansion of the study to recruit an additional 28 patients with PD-1 inhibitor-resistant melanoma. NuCana is currently recruiting patients to this expansion study and plans to meet with the U.S. Food and Drug Administration to discuss the data from this study to determine the optimal registration strategy to support marketing approval.

The details of NuCana’s presentation at ESMO (Free ESMO Whitepaper) are as follows:

Abstract Title: Patient Derived Organoids Reveal Synergy Between NUC-7738 and PD-1 Inhibition in Renal Cell Cancer
Poster Number: 1530P
Session: Investigational Immunotherapy
Date: Sunday, October 19, 2025
Presenting Author: H. Abdullah

(Press release, Nucana, OCT 18, 2025, View Source [SID1234656774])