Abstract 59TiP
Background
Biliary tract cancer (BTC) is an aggressive disease with a poor prognosis. Gemcitabine + cisplatin (GemCis) is the accepted global standard of care; however, key cancer resistance mechanisms associated with the transport, activation and breakdown of gemcitabine are known to limit its clinical activity. NUC-1031 is a phosphoramidate transformation of gemcitabine designed to overcome these key resistance mechanisms and generate much higher levels of the active anti-cancer metabolite, dFdCTP, in cells. Promising efficacy has been observed in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of advanced BTC. Of 21 patients (pts) enrolled in 2 dose cohorts (NUC-1031 625 mg/m2 or 725 mg/m2 + cisplatin 25 mg/m2 on Days 1 and 8 of 21-day cycles), 16 were considered to be efficacy evaluable. In this population, 1 pt had a CR and 6 pts had PRs, resulting in an ORR of 44% (7/16). This compares favorably to the 26% ORR reported for GemCis. In addition, 6 pts had SD, resulting in a DCR of 81% (13/16). The combination was well tolerated with no unexpected AEs or DLTs. The recommended dose of NUC-1031 with cisplatin was 725 mg/m2. The encouraging efficacy and tolerability profile led to initiation of a global registrational study.
Trial design
NuTide:121 is a phase III, open-label, randomised study of NUC-1031 + cisplatin vs GemCis for first-line treatment of advanced BTC. 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, are eligible. A total of 828 pts are being randomised (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 endpoints are OS and ORR. Secondary endpoints include PFS, safety, PK and pt-reported QoL. In addition to the final analysis, three interim analyses are planned. NuTide:121 is being conducted at approximately 125 sites across North America, Europe and Asia Pacific.
Clinical trial identification
NCT04163900.
Editorial acknowledgement
Legal entity responsible for the study
NuCana plc.
Funding
NuCana plc.
Disclosure
J. Knox: Financial Interests, Advisory Role: Lilly; Merck; Financial Interests, Expert Testimony: AstraZeneca; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Research Grant: AstraZeneca; Merck; Ipsen. M.G. McNamara: Financial Interests, Advisory Role: Ipsen; Financial Interests, Research Grant: NuCana; Financial Interests, Speaker’s Bureau: NuCana; Financial Interests, Other, Travel, Accommodations, Expenses: Bayer; Novartis; Financial Interests, Other, Honoraria: Novartis; Financial Interests, Research Grant: Ipsen; Servier; Financial Interests, Advisory Role: Shire; Sirtex Medical. L. Goyal: Financial Interests, Advisory Role: Debiopharm Group; Alentis Therapeutics; QED Therapeutics; H3 Biomedicine; AstraZeneca; Klus Pharma; Agios; Taiho Pharmaceutical; Financial Interests, Other, Travel, Accommodations, Expenses: Taiho Pharmaceutical; Debiopharm Group; Financial Interests, Research Grant: Taiho Pharmaceutical. D. Cosgrove: Financial Interests, Full or part-time Employment: Compass Oncology; Biocompatibles; Financial Interests, Advisory Role: Biocompatibles; Financial Interests, Leadership Role: US Oncology; Financial Interests, Speaker’s Bureau: Biocompatibles; Financial Interests, Other, Travel, Accommodations, Expenses: US Oncology. C. Springfeld: Financial Interests, Advisory Role: Celgene; Servier; Eisai; Roche; MSD; Servier; Financial Interests, Other, Travel, Accommodations, Expenses: Celgene; Servier. K. Sjoquist: Financial Interests, Other, Honoraria: Merck; Amgen; Servier; Bristol-Myers Squibb; Ipsen; Merck; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Advisory Role: Competitive Drug Development. J.O. Park: Financial Interests, Advisory Role: Celgene; Shire; Merck Serono; Sanofi; Servier; AstraZeneca; Financial Interests, Speaker’s Bureau: Celgene; Financial Interests, Research Grant: Celgene. C. Braconi: Financial Interests, Personal, Other, Travel, Accommodations, Expenses received by an immediate family member: Menarini Silicon Biosystems; Financial Interests, Personal, Other, Honoraria received by an immediate family member: Pfizer; Lilly; Merck Serono; Merck Serono; Bayer. P. Ross: Financial Interests, Advisory Role: Sirtex Medical; Eisai; Servier; Pierre Fabre; Shire; Financial Interests, Speaker’s Bureau: Servier; Shire; Shire; Roche; Financial Interests, Other, Travel, Accommodations, Expenses: Bayer; Servier; Bayer; Roche; Financial Interests, Other, Honoraria: Sirtex Medical; Eisai; Servier; Pierre Fabre; Shire; Financial Interests, Institutional, Research Grant: Sanofi; Bayer. D. Oh: Financial Interests, Personal, Advisory Board: AZ; Novartis; Genentech/Roche; Merck Serono; Bayer; Taiho; Halozyme; Zymeworks; BMS/Celegene; Beigene; Turning Point; Basilea; Financial Interests, Personal and Institutional, Research Grant: AZ; Novartis; Array; Eli Lilly; Servier; BeiGene; MSD; Handok. J.R. Zalcberg: Financial Interests, Advisory Role: Pfizer; Merck Serono; Targovax; Merck Sharp & Dohme; Sirtex Medical; Halozyme; Lipotek; Financial Interests, Other, Travel, Accommodations, Expenses: Merck Serono; AstraZeneca; Merck Sharp & Dohme; Deciphera; Financial Interests, Stocks/Shares: GW Pharmaceuticals; Aimmune; Vertex; Bluebird Bio; Alnylam; Biomarin; Sage Therapeutics; Dova Therapeutics; TherapeuticsMD; Juno Therapeutics; Kite Pharma; Kids Pharma; CSL Limited; Cochlear; Financial Interests, Other, Honoraria: Pfizer; Specialised Therapeutics; Merck Serono; Targovax; Halozyme; Gilead Sciences; Financial Interests, Institutional, Research Grant: Bayer; Merck Serono; Roche; Bristol-Myers Squibb; Pfizer; AstraZeneca; Specialised Therapeutics; Baxalta/Shire; Lilly. D. Palmer: Financial Interests, Other, Honoraria: Bayer; Sirtex Medical; AstraZeneca; NuCana; Bristol Myers-Squibb; Financial Interests, Other, Honoraria received by an immediate family member: Eisai Europe; Financial Interests, Advisory Role: Bayer; Sirtex Medical; AstraZeneca; NuCana; Bristol Myers-Squibb; Eisai Europe; Financial Interests, Research Grant: Bayer; Bristol Myers-Squibb; Sirtex Medical; BTG; AstraZeneca; Financial Interests, Other, Travel, Accommodations, Expenses: NuCana. J.W. Valle: Financial Interests, Advisory Role: Ipsen; Novartis; AstraZeneca; Merck; Delcath Systems; Agios; Pfizer; PCI Biotech; Incyte; Keocyt; QED Therapeutics; Pieris Pharmaceuticals; Genoscience Pharma; Mundipharma EDO GmbH; Wren Laboratories; NuCana; Servier; Debiopharm Group; Imaging Equipment Limited; Financial Interests, Speaker’s Bureau: Novartis; Ipsen; NuCana; Imaging Equipment Limited; Financial Interests, Other, Travel, Accommodations, Expenses: Celgene; : NuCana; Pfizer; Financial Interests, Other, Honoraria: Ipsen; Financial Interests, Institutional, Research Grant: Novartis. All other authors have declared no conflicts of interest.