Company: NCNA
Filing Date: 2025-03-20
Form Type: 20-F
Source: 0000950170-25-042709
Chunk: 146

Company: NuCana plc
Filing Date: 2025-03-20
Form: 20-F
Item: Item 4
Chunk 146
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 assessed by Blinded Independent Central Review, was 18.7% (3 Complete Responses and 50 Partial Responses) in the Acelarin plus cisplatin arm and 12.4% (0 Complete Responses and 34 Partial Responses) in the gemcitabine plus cisplatin arm. However, this improvement in ORR was not reflected by an improvement in OS. Median OS was 9.2 months in the Acelarin plus cisplatin arm and 12.6 months in the gemcitabine plus cisplatin arm corresponding to a hazard ratio of 1.79. Treatment exposure was lower in the Acelarin plus cisplatin arm, which may be at least partially explained by a higher discontinuation rate due to treatment emergent adverse events (TEAEs) in the Acelarin plus cisplatin arm (30% vs

16%). More patients discontinued during the first 30 days of treatment in the Acelarin plus cisplatin arm (11% vs 1%) and this was predominantly due to liver-related TEAEs. An evaluation of the liver-related TEAEs observed in this trial suggested that the assessment of drug-induced liver toxicity is potentially confounded by disease progression and the corresponding high frequency of liver dysfunction in patients with advanced biliary tract cancer which are difficult to distinguish from the pattern of drug related liver toxicity. We believe that the pattern of liver-related TEAEs observed in NuTide:121 is specific to biliary tract cancer and potentially the combination with cisplatin. The pattern of liver-related TEAEs observed in NuTide:121 was not observed in trials that assessed Acelarin as a monotherapy (PRO-001, PRO-105 and ACELARATE) or in combination with carboplatin (PRO-002).
 Overall, the Acelarin safety profile was generally similar to that of gemcitabine. The lower treatment exposure in the Acelarin plus cisplatin arm due to adverse event related early discontinuations may partially explain why the increased ORR did not translate into a survival benefit. We are assessing future development options for Acelarin in biliary tract cancer which may explore lower doses of Acelarin, alternative combination partners or specific sub-sets of biliary tract cancer patients. Indications other than biliary tract cancer are also being assessed as future development options for Acelarin.
 Molecular Profiling
 Healthcare professionals often use molecular-profiling tools to help choose the optimal therapy for patients with cancer. Ther