Company: NCNA
Filing Date: 2025-03-20
Form Type: 20-F
Source: 0000950170-25-042709
Chunk: 135

Company: NuCana plc
Filing Date: 2025-03-20
Form: 20-F
Item: Item 4
Chunk 135
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 patients with advanced solid tumors and in combination with docetaxel for patients with lung cancer. In November 2024, we announced Phase 1 data from the NuTide:303 trial. In 2025, we expect to announce data from the NuTide:303 trial of NUC-3373 in combination with pembrolizumab in patients with solid tumors.
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NUC-3373: Completed Phase 1 clinical trial (NuTide:301).

 NUC-3373 has demonstrated a favorable safety and pharmacokinetic profile with promising clinical activity in a Phase 1 clinical trial, also known as the NuTide:301 trial, in patients with advanced solid tumors who had exhausted all treatment options. In this trial, the maximum tolerated dose and schedule was established as 2,500 mg/m2 weekly. In addition, we measured various pharmacokinetic and pharmacodynamic parameters, including plasma concentration of NUC-3373, intracellular concentrations of the active anti-cancer metabolite, FUDR-MP, the ability of NUC-3373 to bind to its target enzyme, TS, and the downstream effects on the levels of dTMP. The anti-cancer mechanism of action of NUC-3373 has been previously observed in preclinical studies, which NuCana believes further supports the biological advantages of NUC-3373 over 5-FU.

 In September 2021, at ESMO, we presented PK data from patients treated with NUC-3373 at doses ranging from 500 mg/m2 to 3,250 mg/m2. The PK profile of NUC-3373 was linear with a dose proportional increase and was reproducible. NUC-3373 also had a long plasma half-life of 6 to 14 hours compared with the half-life of 8 to 14 minutes for 5-FU. Intracellular levels of the active anti-cancer metabolite, FUDR-MP, also increased in a dose proportional manner and were substantially higher than those reported in the literature for 5-FU.

Overall, 59 patients with advanced cancer, who had exhausted all other available treatment options, were enrolled in the trial. This heavily