NuTide:301 Clinical Study

Phase I dose-escalation study in patients with advanced solid tumours

  • All patients have metastatic spread & rapidly progressing disease
  • Exhausted all other therapeutic options
  • Objective: Recommended Phase II Dose + Schedule
NuTide:301 study image of man
Demographic Overall Study
Patients (enrolled to date) 36
Median Age 60 (range 21-78)
Median Prior Chemotherapy Regimens 3 (range 1-6)

Results

NUC-3373 is currently being evaluated in a Phase I clinical study of patients with advanced solid tumours for which we reported interim data in September 2017. Key interim findings include a favourable plasma half-life of 9.7 hours compared to just 8-14 minutes for 5-FU; the ability to completely deplete the intracellular pool of dTMP, along with undetectable levels of the toxic metabolite dhFU.

NUC-3373 PK profile comparison with 5-FU

NUC-3373 5-FU
Plasma half-life 9.7 Hours 8-14 minutes
FUDR-MP (in PBMCs) Detected (dose proportional) Undetected(*)
Thymidylate Synthase inhibition Strong Weak
Intracellular levels of dTMP Depleted No change
Toxic metabolite (dhFU) Levels not clinically significant High levels

* Derissen et al, 2016

To date, 36 patients, all with metastatic cancer, have been enrolled in the study, with 29 patients receiving NUC-3373 on a weekly schedule on days 1, 8, 15 and 22 of a 28-day cycle at doses ranging from 125 mg/m2 to 1,500 mg/m2 and 7 patients receiving NUC-3373 on an alternate-week, or fortnightly, schedule on days 1 and 15 of a 28-day cycle at doses ranging from 1,500 mg/m2 to 1,875 mg/m2.

Both dosing regimens were observed to be well tolerated with no unexpected adverse events (AEs) or accumulative toxicity. Importantly, no patients developed hand-foot syndrome, which is a debilitating side effect associated with fluoropyrimidine therapy. In addition, NUC-3373 has a plasma half-life of 9.7 hours compared to the 8 to 14-minute plasma half-life of 5-FU. As a result, NUC-3373 can be infused over a much shorter time frame of 30 minutes to four hours compared to the 46-hour continuous infusion required with 5-FU.

Notably, three patients achieved Stable Disease after treatment, with responses lasting more than nine months at the time of data cutoff on September 25, 2018:

Colorectal Cancer

70 years, male
6 previous lines of therapy

  1. 1.5-FU based chemoradiotherapy
  2. FOLFIRI for metastatic disease
  3. CAPOX: relapsed within 2 months
  4. FOLFIRI: relapsed within 8 months
  5. LONSURF: relapsed within 3 months
  6. Irinotecan: treatment for 1 month

Cholangiocarcinoma

60 years, femamale
6 previous lines of therapy

  1. Cisplatin + gemcitabine: relaspsed within 6 months

Basal Cell Carcinoma

55 years, males
6 previous lines of therapy

  1. Vismodegib: treatment for 11 months (best response PR)
  2. Paclitaxel + carboplatin: treatment for 3 months (best response PR)

Key Publication

Poster ESMO 2018 (Solid Tumours)

Poster ESMO 2017 (Solid Tumours)

Poster AACR 2016 (Solid Tumours)

Plasma NUC-3373 and Intracellular FUDR-MP pharmacokinetics

NuTide:301 PK data graphs

Standard error of mean