^
    3ms
    A phosphoramidate modification of FUDR, NUC-3373, causes DNA damage and DAMPs release from colorectal cancer cells, potentiating lymphocyte-induced cell death. (PubMed, PLoS One)
    Lastly, the PD-1 immune checkpoint inhibitor nivolumab showed synergistic activity when HCT116 cells were pre-treated with NUC-3373. To conclude, we show that NUC-3373 can modulate immune signaling and may therefore facilitate immune mediated tumour cell death in vitro.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    IFNG (Interferon, gamma) • LAMP1 (Lysosomal Associated Membrane Protein 1)
    |
    Opdivo (nivolumab) • 5-fluorouracil • fosifloxuridine nafalbenamide (NUC-3373)
    5ms
    NuTide:303: NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1/2, N=19, Terminated, NuCana plc | N=91 --> 19 | Trial completion date: Dec 2025 --> May 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> May 2025; The NuTide:303 study was terminated at NuCana's discretion due to refinement of the pipeline strategy. The overall risk benefit assessment of NUC-3373 remains positive and future NUC-3373 studies are under consideration.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • docetaxel • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    9ms
    NuTide:303: NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1/2, N=91, Recruiting, NuCana plc | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • docetaxel • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    1year
    NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1/2, N=91, Recruiting, NuCana plc | Trial primary completion date: Aug 2024 --> Jan 2025
    Trial primary completion date • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • docetaxel • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    over1year
    NuTide:323: A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer (clinicaltrials.gov)
    P2, N=182, Terminated, NuCana plc | Trial completion date: Mar 2025 --> Aug 2024 | Active, not recruiting --> Terminated; A pre-planned initial analysis concluded that the study was unlikely to achieve its primary objective of demonstrating superior progression-free survival. Based on the Steering Committee's recommendation, the Sponsor has closed the study.
    Trial completion date • Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    KRAS wild-type • RAS wild-type • UGT1A1*1*1
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • fosifloxuridine nafalbenamide (NUC-3373)
    over1year
    NuTide:302: A Safety, Pharmacokinetic and Efficacy Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment (clinicaltrials.gov)
    P1/2, N=107, Completed, NuCana plc | Recruiting --> Completed | N=225 --> 107 | Trial completion date: Nov 2023 --> Mar 2024 | Trial primary completion date: Nov 2023 --> Mar 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • KRAS wild-type • RAS wild-type
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Vectibix (panitumumab) • oxaliplatin • irinotecan • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    over1year
    A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer (clinicaltrials.gov)
    P2, N=182, Active, not recruiting, NuCana plc | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    KRAS wild-type • RAS wild-type • UGT1A1*1*1
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • fosifloxuridine nafalbenamide (NUC-3373)
    almost2years
    A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer (clinicaltrials.gov)
    P2, N=171, Recruiting, NuCana plc | Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    KRAS wild-type • RAS wild-type • UGT1A1*1*1
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • fosifloxuridine nafalbenamide (NUC-3373)
    over2years
    NuTide:302: A Safety, Pharmacokinetic and Efficacy Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment (clinicaltrials.gov)
    P1/2, N=225, Recruiting, NuCana plc | Trial completion date: Jun 2023 --> Nov 2023 | Trial primary completion date: Jun 2023 --> Nov 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • KRAS wild-type • RAS wild-type
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Vectibix (panitumumab) • oxaliplatin • irinotecan • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    over2years
    NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1/2, N=91, Recruiting, NuCana plc | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • docetaxel • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    over2years
    A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer (clinicaltrials.gov)
    P2, N=171, Recruiting, NuCana plc | Initiation date: Jan 2023 --> Apr 2023
    Trial initiation date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    KRAS wild-type • RAS wild-type • UGT1A1*1*1
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • fosifloxuridine nafalbenamide (NUC-3373) • levoleucovorin calcium
    over2years
    The novel anti-cancer fluoropyrimidine NUC-3373 is a potent inhibitor of thymidylate synthase and an effective DNA-damaging agent. (PubMed, Cancer Chemother Pharmacol)
    Taken together, these results highlight key differences between NUC-3373 and 5-FU that are driven by the anti-cancer metabolites generated. NUC-3373 is a potent inhibitor of TS that also causes DNA-directed damage. These data support the preliminary clinical evidence that suggest NUC-3373 has a favorable safety profile in patients.
    Journal
    |
    TYMS (Thymidylate Synthetase)
    |
    5-fluorouracil • fosifloxuridine nafalbenamide (NUC-3373)