Abstract 566TiP
Background
NUC-7738 is a phosphoramidate transformation of 3’-deoxyadenosine (3’-dA or cordycepin), a derivative of adenosine that was first isolated from Cordyceps sinensis. Although 3’-dA has potent in vitro anti-tumour activity, it has not been successfully developed in the clinic as an anti-cancer agent due primarily to its rapid breakdown by adenosine deaminase (ADA). Although the cytotoxic activity of 3’-dA is largely attributed to intracellular generation of the triphosphate metabolite, 3’-dATP, (inhibition of RNA and DNA synthesis) additional in vitro effects have also been attributed to 3’-dAMP and 3’-dADP. NUC-7738 was designed to overcome the key cancer resistance mechanisms associated with 3’-dA. NUC-7738 is resistant to breakdown by ADA, enters cancer cells independently of the human equilibrative nucleoside transporter (hENT1) and does not require phosphorylation by adenosine kinase.
Trial design
NuTide:701 is a two-part, first-in-human phase I study in patients with advanced solid tumours or lymphoma who have exhausted all standard treatment options. The primary objectives are to: i) assess the safety and tolerability of NUC-7738; and ii) determine the recommended phase II dose (RP2D) and schedule. Secondary objectives include pharmacokinetics and anti-tumour activity. Part 1 will establish the RP2D and schedule of NUC-7738 in patients with advanced solid tumours. Part 2 will further evaluate NUC-7738 in expansion cohorts of patients with advanced solid tumours or lymphomas. Recruitment into Part 1 is currently ongoing across three sites in the UK. A translational program will further establish the pharmacodynamic effects of NUC-7738 and its metabolites in tumour tissue and PBMCs.
Clinical trial identification
NCT03829254.
Editorial acknowledgement
Legal entity responsible for the study
NuCana plc.
Funding
NuCana plc.
Disclosure
S. Blagden: Financial Interests, Personal, Other, Honoraria: NuCana; Financial Interests, Personal, Advisory Role: Ellipses Pharma; Financial Interests, Personal, Research Grant: NuCana; Financial Interests, Personal, Research Grant: Sierra Oncology; Financial Interests, Personal, Research Grant: Astex Pharmaceuticals; Financial Interests, Personal, Research Grant: Incyte; Financial Interests, Personal, Research Grant: Octimet; Financial Interests, Personal, Research Grant: Tesaro; Financial Interests, Personal, Research Grant: Redx Pharma; Financial Interests, Personal, Research Grant: UCB; Financial Interests, Personal, Research Grant: MSD Brazil; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Royalties: RNA Guardian; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: NuCana; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Tesaro. F. Aroldi: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: NuCana. M. Myers: Financial Interests, Personal, Full or part-time Employment: NuCana plc. S.N. Symeonides: Financial Interests, Institutional, Advisory Role: Vaccitech; Financial Interests, Institutional, Advisory Role: Bicycle Therapeutics; Financial Interests, Institutional, Advisory Role: Ellipses Pharma; Financial Interests, Institutional, Advisory Role: EUSA Pharma; Financial Interests, Institutional, Advisory Role: Eisai; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Pfizer/EMD Serono; Financial Interests, Institutional, Advisory Role: MedAnnex; Financial Interests, Institutional, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Speaker’s Bureau: Bristol Myers-Squibb; Financial Interests, Institutional, Speaker’s Bureau: EUSA Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers-Squibb; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Verastem; Financial Interests, Institutional, Research Grant: Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sierra Oncology; Financial Interests, Institutional, Research Grant: NuCana; Financial Interests, Institutional, Research Grant: BioNTech AG; Financial Interests, Institutional, Research Grant: BiolineRx; Financial Interests, Institutional, Research Grant: Nouscom; Financial Interests, Institutional, Research Grant: Sapience Therapeutics. R. Plummer: Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Astex Pharmaceuticals; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Bayer Health; Financial Interests, Personal, Advisory Role: Octimet; Financial Interests, Personal, Advisory Role: Biosceptre; Financial Interests, Personal, Advisory Role: Ellipses Pharma; Financial Interests, Personal, Advisory Role: Karus Therapeutics; Financial Interests, Personal, Advisory Role: Cybrexa Therapeutics; Financial Interests, Personal, Advisory Role: Sanofi/Aventis; Financial Interests, Personal, Advisory Role: CV6 Therapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers-Squibb; Financial Interests, Institutional, Other, Named on patent of use of PARP inhibitor rucaparib: Clovis Oncology; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria received by an immediate family member: Pfizer; Financial Interests, Personal, Other, Honoraria received by an immediate family member: Amgen; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Novartis Pharmaceuticals UK Ltd.; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune. All other authors have declared no conflicts of interest.