A Phase 1/2 interventional study of Fosifloxuridine Nafalbenamide and Leucovorin in Advanced Cancer, Advanced Solid Tumor and Neoplasm Malignant, sponsored by NuCana plc. Terminated at 4 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-23.
Sponsored by NuCana plc · Phase 1/2, Interventional, and Treatment
This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types.
Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II).
Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients.
Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy).
Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease.
The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.
10,818 studies on the registry are indexed under Neoplasms; 2,324 are open to participants now.
This study's enrollment of 19 is below the median of 60 across 7,703 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →NuCana plc is the lead sponsor of 6 studies on the registry; 1 is open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Additional Module 1 Inclusion Criteria:
Additional Module 2 Inclusion Criteria:
Exclusion Criteria (all modules):
Chemotherapy, hormonal therapy, radiotherapy (other than a short cycle of palliative radiotherapy, e.g., for bone pain*), immunotherapy, biological agents, or exposure to another agent within 21 days (or four times the half-life for molecular targeted agents, whichever is shorter) of first administration of study treatment:
Presence of any uncontrolled concurrent serious illness, medical condition or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's ability to participate in the study or with the interpretation of the results, including any of the following:
Additional Module 1 Exclusion Criteria:
Additional Module 2 Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This Module is designed to evaluate the tolerability and the overall safety profile of NUC-3373 (1875 mg/m2) + LV (400 mg/m2) + pembrolizumab (200 mg) in the treatment of patients with advanced solid tumours (dose validation phase). NUC-3373 and LV will be administered on Days 1, 8 and 15 and pembrolizumab will be administered on Day 1 of 21-day cycles. The dosing schedule may be adjusted based on emerging data with agreement from the Safety Review Committee. Following completion of the dose validation phase, expansion cohorts may be initiated at the selected dose level.
Drug: Fosifloxuridine Nafalbenamide · Drug: Leucovorin · Drug: Pembrolizumab
This Module is designed to assess NUC-3373 (750 mg/m2) + LV (400 mg/m2) + docetaxel (55 mg/m2) for the treatment of patients with advanced/metastatic NSCLC or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease (dose validation phase). NUC-3373 and LV will be administered on Days 1 and 22 and docetaxel will be administered on Day 8 of 28-day cycles. The dosing schedule may be adjusted based on emerging data with agreement from the Safety Review Committee. Following completion of the dose validation phase, expansion cohorts may be initiated at the selected dose level.
Drug: Fosifloxuridine Nafalbenamide · Drug: Leucovorin · Drug: Docetaxel
Intravenous infusion
Also known as: NUC-3373, Nucleotide analogue
Intravenous infusion
Also known as: Folinic acid, Levo-leucovorin
Intravenous infusion
Also known as: Keytruda
Intravenous infusion
Also known as: Taxotere, Docecad, Docefrez
Number of Participants With DLTs in Each Module
The outcome measure presented is the number of DLTs per module
Time frame: Assessed during Cycle 1 (first 28 days) in Module 1 and during Cycles 1 and 2 (first 56 days) in Module 2
Number of Patients Achieving a Reduction in Tumour Volume (Objective Response Rate; ORR)
Objective response rate, defined as the percentage of patients achieving a complete (CR) or partial response (PR) to treatment. Response was measured by MRI scan and assessed per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria in Module 2 and by immune RECIST (iRECIST) criteria in Module 1: CR= disappearance of all target lesions PR= at least a 30% decrease in the sum of the longest diameter of target lesions
Time frame: Assessed from baseline to 30 days after last dose of study drug, up to 20 months
Number of Patients Achieving a Reduction or Stabilisation in Tumor Volume (Disease Control Rate; DCR)
Disease control rate, defined as the number of patients achieving a response (CR or PR) or stable disease (SD) as their best overall response. Disease control was measured by MRI scan and assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria in Module 2 and immune RECIST (iRECIST) criteria in Module 1: CR= disappearance of all target lesions PR= at least a 30% decrease in the sum of the longest diameter of target lesions SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease
Time frame: Assessed from baseline to 30 days after the last dose of study drug, up to 20 months
A total of 26 patients were screened and 19 patients were enrolled across 3 sites in the UK between March 2023 and May 2025.
| Milestone | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| Started | 15 | 4 |
| Completed | 2 | 0 |
| Not completed | 13 | 4 |
| Withdrew: Progressive disease | 9 | 3 |
| Withdrew: Not treated | 2 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Adverse event | 1 | 0 |
The outcome measure presented is the number of DLTs per module
| Participants | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| Number of Participants With DLTs in Each Module | 0 | 0 |
Objective response rate, defined as the percentage of patients achieving a complete (CR) or partial response (PR) to treatment. Response was measured by MRI scan and assessed per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria in Module 2 and by immune RECIST (iRECIST) criteria in Module 1: CR= disappearance of all target lesions PR= at least a 30% decrease in the sum of the longest diameter of target lesions
| Participants | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| Number of Patients Achieving a Reduction in Tumour Volume (Objective Response Rate; ORR) | 2 | 0 |
Disease control rate, defined as the number of patients achieving a response (CR or PR) or stable disease (SD) as their best overall response. Disease control was measured by MRI scan and assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria in Module 2 and immune RECIST (iRECIST) criteria in Module 1: CR= disappearance of all target lesions PR= at least a 30% decrease in the sum of the longest diameter of target lesions SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease
| Participants | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| Number of Patients Achieving a Reduction or Stabilisation in Tumor Volume (Disease Control Rate; DCR) | 6 | 2 |
Collected over Each patient was assessed for adverse events from the date of informed consent until 30 days after the last dose of study drug, up to 20 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Module 1 (NUC-3373 + LV + Pembrolizumab) | 10/13 (76.9%) | 7/13 (53.8%) | 13/13 (100%) |
| Module 2 (NUC-3373 + LV + Docetaxel) | 3/4 (75%) | 3/4 (75%) | 4/4 (100%) |
| Event | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| VomitingGastrointestinal disorders | 1/13 | 1/4 |
| InfectionInfections and infestations | 0/13 | 1/4 |
| PyrexiaGeneral disorders | 0/13 | 1/4 |
| DiarrheaGastrointestinal disorders | 0/13 | 1/4 |
| HypercalcemiaMetabolism and nutrition disorders | 0/13 | 1/4 |
| Abdominal pain upperGastrointestinal disorders | 1/13 | 0/4 |
| DizzinessNervous system disorders | 1/13 | 0/4 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/13 | 0/4 |
| Kidney infectionInfections and infestations | 1/13 | 0/4 |
| PneumoniaInfections and infestations | 1/13 | 0/4 |
| Event | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) |
|---|---|---|
| VomitingGastrointestinal disorders | 9/13 | 1/4 |
| NauseaGastrointestinal disorders | 9/13 | 2/4 |
| DiarrheaGastrointestinal disorders | 7/13 | 2/4 |
| AnemiaBlood and lymphatic system disorders | 7/13 | 1/4 |
| ConstipationGastrointestinal disorders | 6/13 | 2/4 |
| Abdominal painGastrointestinal disorders | 2/13 | 2/4 |
| StomatitisGastrointestinal disorders | 0/13 | 2/4 |
| C-reactive protein increasedInvestigations | 0/13 | 2/4 |
| HypomagnesemiaMetabolism and nutrition disorders | 4/13 | 2/4 |
| Decreased appetiteMetabolism and nutrition disorders | 2/13 | 2/4 |
| Age, Continuous(Years) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| Median | 69.0 (49 to 77) | 67.5 (60 to 76) | 69.0 (49 to 77) |
| Sex: Female, Male(Participants) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| Female | 3 | 2 | 5 |
| Male | 12 | 2 | 14 |
| Race (NIH/OMB)(Participants) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 14 | 4 | 18 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Primary tumor location(Participants) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| Cutaneous melanoma | 3 | 0 | 3 |
| Bladder (urothelial) | 2 | 0 | 2 |
| Oropharyngeal | 2 | 0 | 2 |
| NSCLC | 3 | 3 | 6 |
| Pleural mesothelioma | 1 | 1 | 2 |
| Anal | 1 | 0 | 1 |
| Sinonasal | 1 | 0 | 1 |
| Pancreatic | 1 | 0 | 1 |
| Rectal | 1 | 0 | 1 |
| Tumor stage(Participants) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| Stage I | 1 | 0 | 1 |
| Stage III | 7 | 0 | 7 |
| Stage IV | 4 | 4 | 8 |
| Unknown | 2 | 0 | 2 |
| Stage II | 1 | 0 | 1 |
| ECOG performance status(Participants) | Module 1 (NUC-3373 + LV + Pembrolizumab) | Module 2 (NUC-3373 + LV + Docetaxel) | Total |
|---|---|---|---|
| 0 | 5 | 1 | 6 |
| 1 | 10 | 3 | 13 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2023 to primary completion in May 2025, 26 months.
Results were first posted in Jul 2026, 1 year 1 month after primary completion.
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Studies of the drug tested here: Fosifloxuridine nafalbenamide
NuCana plc