A study of NUC-3373 in combination with other agents in patients with advanced solid tumours
Research type
Research Study
Full title
A Phase Ib/II open label, multi-arm, parallel cohort dose finding and expansion study to assess the safety, pharmacokinetics and efficacy of NUC-3373, a nucleotide analogue, given in combination with standard approved agents in patients with advanced solid tumours
IRAS ID
1005243
Contact name
Stuart Grant
Contact email
Sponsor organisation
NuCana plc
Eudract number
2022-000722-14
Clinicaltrials.gov Identifier
Research summary
The purpose of this study is to learn more about the effects (safety, effectiveness and tolerability) of a new drug called NUC-3373 in
combination with other medicines that are approved for the treatment of patients with advanced solid tumours. The study will
determine the best dose and schedule of NUC-3373 to be used in combination with these other treatments.There are different parts to this study, known as modules. In all modules, NUC-3373 will be given with an agent called leucovorin
(LV). LV is folinic acid (made from B vitamins) and is given in combination with certain cancer drugs to improve anti-cancer
activity.In Module 1, NUC-3373 + LV will be given to participants with an advanced solid tumour that has returned after previous
treatment with anti-cancer therapies, in combination with pembrolizumab, an immunotherapy drug.In Module 2, NUC-3373 + LV will be given in combination with docetaxel to participants with advanced or metastatic non-small
cell lung cancer (NSCLC) that has returned after previous treatment with other anti-cancer therapies, or who have been unable to
tolerate previous anti-cancer therapies.LAY SUMMARY OF STUDY RESULTS:
"The Sponsor of this study developed a new type of chemotherapy called NUC 3373. They wanted to learn about the safety and anti-cancer activity (how a tumour responds to a drug) of NUC-3373 when given in combination with other medicines. The study was split into two modules. In both modules, NUC-3373 was given with leucovorin (LV), which is also known as folinic acid.
In Module 1, NUC-3373 + LV was given in combination with the immunotherapy medicine pembrolizumab in patients with advanced solid tumours.
In Module 2, NUC-3373 + LV was given in combination with the chemotherapy medicine docetaxel in patients with lung cancer or pleural mesothelioma.
In each module, two phases were planned; Phase Ib and Phase II. In May 2025, the sponsor decided to stop the study early; therefore, the Phase II part of each module was not started. This summary presents the main results from the Phase Ib part.
In Module 1, 13 people (49 to 77 years old) with advanced solid tumours participated in this study.
In Module 2, 4 people (60 to 76 years old) with lung cancer or pleural mesothelioma participated in this study.
The study took place at 3 hospitals in the UK between March 2023 and May 2025.
This was an open-label study, which means the study doctors and participants knew which treatments participants were receiving.
In Module 1, participants received these treatments:
• NUC-3373 (1875 mg/m2) + LV (400 mg/m2) on Days 1, 8 and 15 of a 21-day cycle
• Pembrolizumab (200 mg) on Day 1 of a 21-day cycle
In Module 2, participants received these treatments:
• NUC-3373 (750 mg/m2) + LV (400 mg/m2) on Days 1 and 22 of a 28-day cycle
• Docetaxel (55 mg/m2) on Day 8 of a 28-day cycle
During the study, the participants visited the study clinic on Days 1, 8 and 15 of each 21-day cycle (in Module 1) or on Days 1, 8, 15 and 22 of each 28-day cycle (in Module 2). On these visits, the participants received the study treatments and underwent tests to make sure it was safe for them to continue in the study.
This is a summary of the main results from the Phase Ib part of the study. These are the results from all the participants combined for each module. The individual results of each participant might be different and are not in this summary.
To answer the main aim of the study and find the best dose of the study drugs, researchers checked how many participants had certain severe side-effects called dose-limiting toxicities (DLTs) in each dose group studied:
• Module 1: no participants had DLTs in the first 6 participants treated with NUC-3373 at 1875 mg/m2 in combination with LV and pembrolizumab
• Module 2: no participants had DLTs in the first 4 participants treated with NUC-3373 at 750 mg/m2 in combination with LV and docetaxel. However, other side effects experienced by participants stopped the dose of NUC-3373 from being increased to a level with known anti-cancer activity and the module was put on hold.
Based on these findings, it was decided that the recommended dose for Module 1 is NUC-3373 1875 mg/m2 + LV 400 mg/m2 + pembrolizumab 200 mg. A recommended dose could not be found in Module 2 due to side effects.
Below is a summary of the side-effects participants had during the study that the study doctors thought might be related to the study treatments. In this summary, these side-effects are called “adverse reactions”. This summary also includes information about serious adverse reactions. An adverse reaction is considered “serious” when it is life-threatening, causes lasting problems, or requires hospital care.
The number and percentage of participants who had serious adverse reactions was:
• Module 1: 7 participants (54%)
• Module 2: 3 participants (75%)
In Module 1, one patient (8%) each had the following serious adverse reactions: upper abdominal pain, dizziness, dyspnoea, kidney infection, pneumonia, spinal cord compression and vomiting.
In Module 2, one patient (25%) each had the following serious adverse reactions: vomiting, infection, pyrexia, diarrhoea, and hypercalcemia.
The number and percentage of participants who had any adverse reactions was:
• Module 1: 13 participants (100%)
• Module 2: 4 participants (100%)
The most common adverse reactions in Module 1 were vomiting (77%), nausea (69%), fatigue (46%), diarrhoea (39%), anaemia (31%), increased levels of liver enzymes called ALT and AST (31%), and constipation (23%). The most common adverse reactions in Module 2 were fatigue (100%), nausea (50%), diarrhoea (50%), mouth sores (50%), and hypotension (50%).
Other studies may or may not show that these side-effects were related to the study treatments. The results from several studies are often needed to decide what side-effects are actually caused by a treatment.
The results of this study have helped researchers learn more about using NUC-3373 + pembrolizumab in people with advanced solid tumours and NUC-3373 + docetaxel in people with lung cancer or pleural mesothelioma."REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
22/WM/0238
Date of REC Opinion
7 Dec 2022
REC opinion
Further Information Favourable Opinion