Phase III study of NUC-1031+cisplatin vs gemcitabine plus cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121)
Authors
Knox, J. J.McNamara, Mairead G
Goyal, L.
Cosgrove, D.
Springfeld, C.
Sjoquist, K. M.
Park, J. O.
Verdaguer, H.
Braconi, C.
Ross, P. J.
De Gramont, A.
Shroff, R. T.
Zalcberg, J. R.
Palmer, D. H.
Valle, Juan W
Affiliation
Princess Margaret Cancer Center, University Health Network, Toronto, ON, CanadaIssue Date
2021
Metadata
Show full item recordAbstract
Background: Biliary tract cancer (BTC) carries a poor prognosis and no first-line treatments are approved. The accepted global standard of care is gemcitabine + cisplatin (GemCis). NUC-1031 is a phosphoramidate transformation of gemcitabine designed to overcome key cancer resistance mechanisms that are associated with gemcitabine. Promising efficacy has been observed with single-agent NUC-1031 in a phase I study in advanced solid tumors and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of advanced BTC. Of 14 patients enrolled in 2 cohorts (NUC-1031 625 mg/m2 or 725 mg/m2 + cisplatin 25 mg/m2 on Days 1 and 8 of 21-day cycle), 1 had a CR and 6 had PRs, resulting in an unconfirmed ORR of 50%. This represents an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected AEs or DLTs. The RP2D of NUC-1031 with cisplatin was 725 mg/m2. The tolerability profile, together with encouraging efficacy, suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for BTC and led to initiation of a global registrational study. Methods: NuTide:121 is a Phase III, open-label, randomized study of NUC-1031 + cisplatin vs GemCis for first-line treatment of advanced BTC. Patients ≥18 years with histologically- or cytologically-confirmed BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease, are eligible. A total of 828 patients are being randomized (1:1) to either 725 mg/m2 NUC-1031 or 1000 mg/m2 gemcitabine, both with 25 mg/m2 cisplatin, administered on days 1 and 8 of 21-day cycles. Primary objectives are OS and ORR. Secondary objectives include PFS, safety, PK and patient-reported quality of life. In addition to the final analysis, three interim analyses, including two designed to support accelerated approval, are planned. The study has passed an initial safety analysis, with no protocol changes required. NuTide:121 is being conducted at approximately 130 sites across North America, Europe and Asia Pacific countries.Citation
Knox JJ, McNamara MG, Goyal L, Cosgrove D, Springfeld C, Sjoquist KM, et al. Phase III study of NUC-1031 + cisplatin vs gemcitabine + cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121). JCO. 2021 Jan 20;39(3_suppl):TPS351–TPS351.Journal
Journal of Clinical OncologyDOI
10.1200/JCO.2021.39.3_suppl.TPS351Additional Links
https://dx.doi.org/10.1200/JCO.2021.39.3_suppl.TPS351Type
Meetings and ProceedingsLanguage
enae974a485f413a2113503eed53cd6c53
10.1200/JCO.2021.39.3_suppl.TPS351