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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

5616 - A new ProTide, NUC-1031, combined with cisplatin for the first-line treatment of advanced biliary tract cancer (ABC-08)

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Clinical Research

Tumour Site

Hepatobiliary Cancers

Presenters

Mairead McNamara

Citation

Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282

Authors

M.G. McNamara1, J. Bridgewater2, D. Palmer3, H. Wasan4, W..D. Ryder5, C. Gnanaranjan6, E. Ghazaly7, T.R..J. Evans8, J.W. Valle1

Author affiliations

  • 1 Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2 Oncology, University College London Hospitals, London/GB
  • 3 Medical Oncology, Clatterbridge Cancer Centre, CH634JY - Liverpool/GB
  • 4 Medical Oncology, Imperial College London - Hammersmith Hospital, W12 0HS - London/GB
  • 5 Mahsc-ctu, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 6 Cancer Institute, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 7 Centre For Haemato-oncology, Barts Cancer Centre, EC1M6BQ - London/GB
  • 8 Institute Of Cancer Sciences, Beatson Institute for Cancer Research, G61 1BD - Glasgow/GB
More

Resources

Abstract 5616

Background

Cisplatin + gemcitabine (cis/gem) is the global standard of care for 1st-line treatment of patients (pts) with locally advanced/metastatic biliary tract cancer (BTC). No agents have regulatory approval for this disease. Cis/gem achieves an objective response rate (ORR) of 26% and median overall survival (OS) of 11.7 months (ABC-02). Inherent/acquired resistance mechanisms limit gemcitabine efficacy. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome resistance mechanisms associated with poor gemcitabine response.

Methods

Pts with locally advanced/metastatic BTC, ECOG PS of 0-1 and no prior systemic therapy received NUC-1031 (625 or 725 mg/m2) combined with cisplatin (25 mg/m2) on days 1 + 8 every 21 days. Primary endpoints: safety and determination of RP2D. Secondary endpoints: ORR, pharmacokinetics, progression-free and OS.

Results

14 pts (median age 61 yrs, 8 male; 5 hilar, 4 distal bile duct, 2 intrahepatic, 2 ampullary and 1 gallbladder) were enrolled across cohorts 1 (625 mg/m2, n = 8) and 2 (725 mg/m2, n = 6). 11 pts completed >1 cycle and were efficacy evaluable, receiving a median of 6.5 cycles (range 3.5-12). ORR was 64% (1 CR, 6 PRs) and DCR: 73%. PFS/OS data collection is ongoing. High, durable intracellular levels of the active anti-cancer metabolite dFdCTP were generated in PBMCs (t1/2=22 h). Treatment was well tolerated with no unexpected AEs/DLTs. Grade 3 TEAEs included neutropenia (14%), fatigue (14%), pyrexia (14%), ALT (7%), AST (7%), GGT (7%) and nausea (7%). Based on high response rate and favourable safety profile, 625 mg/m2 was deemed RP2D. An expansion cohort is ongoing (n = 6).Table: 758P

ITTEfficacy evaluable
625 mg/m2 (n = 8) n (%)725 mg/m2 (n = 6) n (%)Total (n = 14) n (%)625 mg/m2 (n = 6) n (%)725 mg/m2 (n = 5) n (%)Total (n = 11) n (%)
CR1 (13)0 (0)1 (7)1 (17)0 (0)1 (9)
PR3 (38)3 (50)6 (43)3 (50)3 (60)6 (55)
ORR4 (50)3 (50)7 (50)4 (67)3 (60)7 (64)
SD0 (0)1 (17)1 (7)0 (0)1 (20)1 (9)
DCR4 (50)4 (67)8 (57)4 (67)4 (80)8 (73)

Conclusions

NUC-1031 + cisplatin demonstrated a very high ORR, with a favourable safety profile, and may provide an improved treatment option over cis/gem for advanced BTC. Further development of NUC-1031 in BTC is planned.

Clinical trial identification

NCT02351765.

Legal entity responsible for the study

The Christie NHS Foundation Trust.

Funding

NuCana.

Editorial Acknowledgement

Not applicable.

Disclosure

All authors have declared no conflicts of interest.

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