Abstract 80TiP
Background
The prognosis for patients (pts) with biliary tract cancer (BTC) is poor with no approved first-line treatments. Although gemcitabine + cisplatin (GemCis) is accepted as the global standard of care (SoC) for treatment of advanced BTC, the reported unconfirmed ORR and OS from randomised studies are low at 18-26% and 11.2-11.7 months, respectively. NUC-1031, a phosphoramidate transformation of the active metabolite of gemcitabine, is designed to overcome key cancer resistance mechanisms associated with gemcitabine. Promising efficacy has been achieved with single-agent NUC-1031 in a phase I study in advanced solid tumours and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of pts with advanced BTC. Of 14 pts enrolled, 1 achieved a CR and 6 achieved PR, giving an unconfirmed ORR of 50%, representing an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected AEs or dose-limiting toxicities. The tolerability profile together with robust efficacy signals suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for pts with advanced BTC and led to initiation of a global registrational study, NuTide:121.
Trial design
A phase III, open-label, randomised study of NUC-1031 + cisplatin versus GemCis for first-line treatment of advanced BTC includes pts ≥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. 828 pts are being randomised (1:1) to either NUC-1031 (725 mg/m2) + cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2) + cisplatin (25 mg/m2), administered on Days 1 and 8 of a 21-day cycle. Primary objectives are OS and ORR. Secondary objectives include PFS, safety, PK, pt-reported quality of life and correlative studies. Three interim analyses, including two designed to support accelerated approval, are planned, in addition to the final analysis. The study is being conducted at approximately 120 sites across North America, Europe and Asia Pacific countries.
Clinical trial identification
NCT04163900.
Editorial acknowledgement
Legal entity responsible for the study
NuCana plc.
Funding
NuCana plc.
Disclosure
J.J. Knox: Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Honoraria (self): Novartis; Research grant/Funding (self): Ipsen. M.G. McNamara: Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Shire; Advisory/Consultancy: Sirtex Medical; Speaker Bureau/Expert testimony, Research grant/Funding (self): NuCana; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Novartis; Research grant/Funding (self): Servier. L. Goyal: Advisory/Consultancy, Travel/Accommodation/Expenses: Debiopharm Group; Advisory/Consultancy: Alentis Therapeutics; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: H3 Biomedicine; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Klus Pharma; Advisory/Consultancy: Agios; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Taiho Pharmaceutical. M. Doherty: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Roche Canada; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy: Eisai; Advisory/Consultancy: Boehringer Ingelheim. D. Cosgrove: Full/Part-time employment: Compass Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Full/Part-time employment: Biocompatabilites; Leadership role, Travel/Accommodation/Expenses: US Oncology. C. Springfeld: Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD. K. Sjoquist: Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Servier; Honoraria (institution): Bristol-Myers-Squibb; Research grant/Funding (institution): Bayer. J.O. Park: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy: Shire; Advisory/Consultancy: Merck Sereno; Advisory/Consultancy: Sanofi; Advisory/Consultancy: SERVIER; Advisory/Consultancy: AstraZeneca. C. Braconi: Travel/Accommodation/Expenses: Menarini Silicon Biosystems; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self): Merck Serono; Honoraria (self): Bayer. P. Ross: Honoraria (self), Advisory/Consultancy: Sirtex Medical; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: SERVIER; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Sanofi. J.R. Zalcberg: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy: Targovax; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Sirtex Medical; Honoraria (self), Advisory/Consultancy: Halozyme; Advisory/Consultancy: Lipotek; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Deciphera; Shareholder/Stockholder/Stock options: GW Pharmaceuticals; Shareholder/Stockholder/Stock options: Aimmune; Shareholder/Stockholder/Stock options: Vertex; Shareholder/Stockholder/Stock options: Bluebird Bio; Shareholder/Stockholder/Stock options: Alnylam; Shareholder/Stockholder/Stock options: Biomarin; Shareholder/Stockholder/Stock options: Sage Therapeutics; Shareholder/Stockholder/Stock options: Dova Pharmaceuticals; Shareholder/Stockholder/Stock options: TherapeuticsMD; Shareholder/Stockholder/Stock options: Juno Therapeutics; Shareholder/Stockholder/Stock options: Kita Pharma; Shareholder/Stockholder/Stock options: Kiadis Pharma; Shareholder/Stockholder/Stock options: CSL Limited; Shareholder/Stockholder/Stock options: Cochlear; Honoraria (self), Research grant/Funding (institution): Specialised Therapeutics; Honoraria (self): Gilead Sciences; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Baxalta/Shire; Research grant/Funding (institution): Lilly. D. Palmer: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sirtex Medical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: NuCana; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Eisai Europe Ltd; Research grant/Funding (self): BTG. J.W. Valle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: Agios; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyte; Advisory/Consultancy: QED Therapeutcs; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Mundipharma EDO GmbH; Advisory/Consultancy: Wren Laboratories; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: NuCana; Advisory/Consultancy: SERVIER; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Limited; Travel/Accommodation/Expenses: Celgene. All other authors have declared no conflicts of interest.