Advanced CancerPhase 1/2NCT03829254
A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma
A Phase 1/2 study testing NUC-7738 and Pembrolizumab in people with Advanced Cancer and Lymphoma, run by NuCana plc at 9 sites in United Kingdom.
Trial summary
This is a Phase I/II, dose-escalation and expansion study of NUC-7738 administered by intravenous infusion as a monotherapy and in combination with pembrolizumab. In Phase I, NUC-7738 monotherapy is evaluated across two administration schedules (weekly or fortnightly) in a dose-escalation design in patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Lymphoma, Solid Tumor
- What is being tested?
- NUC-7738 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- 17 Jun 2019to Aug 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed written informed consent.
- Solid tumour cohorts only (Phase I and Phase II; excluding NUC-7738 + pembrolizumab cohort): Histologically confirmed diagnosis of an advanced solid tumour with measurable disease as per RECIST v1.1 criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions, which do not fulfil RECIST v1.1 criteria for measurable disease) for solid tumours.
- NUC-7738 + pembrolizumab cohort only (Phase II): Histologically confirmed diagnosis of metastatic cutaneous melanoma with measurable disease as per RECIST v1.1 criteria. Must have progressed on ≤2 prior lines of therapy for advanced/metastatic disease. In addition, patients may have been treated in the neoadjuvant/adjuvant setting. At least one prior line must have included a PD-1/PD-L1-containing regimen (either monotherapy or in combination) for which they progressed on.
- Lymphoma cohort only (Phase II): Relapsed refractory lymphoma (high grade and low grade B-NHL, Hodgkin's Lymphoma and T-cell lymphomas), which is not amenable to standard of care, is refractory to standard of care or for which no standard of care exists. Patients must have bi-dimensionally measurable disease as per Cheson et al, 2007 criteria for lymphoma.
- For solid tumours in single-agent Phase II cohorts only: patients should have received no more than 3 prior lines of treatment for metastatic disease.
- Age ≥18 years (no upper age limit).
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- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Life expectancy of ≥12 weeks.
- Adequate bone marrow, liver, and renal function.
- Ability to comply with protocol requirements.
- Female patients of child-bearing potential must have a negative serum pregnancy test within 3 days prior to the first NUC-7738 administration. All patients of child-bearing potential must agree to practice true abstinence or to use two forms of contraception, one of which must be a highly effective method of contraception, from the time of screening until 6 months after the last dose of study medication.
- Phase I and Phase II dose-confirmation cohorts only: Patient must be willing to undergo a new tumour biopsy at Screening and during therapy on the study. Biopsies are mandatory for patient inclusion, except where taking a biopsy would be associated with unacceptable clinical risk due to the location of the disease. Such patients may be discussed on a case-by-case basis with the study Medical Monitor to determine their eligibility. A prior (archival) biopsy that is less than 3 months old may be substituted for a fresh tumour biopsy at Screening with agreement from the Medical Monitor. From protocol v3.4 onwards, biopsies are no longer required.
- Patients must have been advised to take measures to avoid or minimise exposure of the skin and eyes to UV light, including avoiding sunbathing and visits to the solarium, for the duration of study participation and for a period of 4 weeks following the last dose of study medication.
Who cannot join
- The following exclusion criteria apply to all patients. Please also refer to additional exclusion criteria for the NUC-7738 + pembrolizumab cohort below.
- History of allergic reaction fo any of the components of NUC-7738.
- Central nervous system or leptomeningeal metastases. Patients with brain metastases are eligible if they have no ongoing neurological symptoms, have not received corticosteroids within 7 days prior to enrolment, and show radiographic stability for at least 2 weeks.
- Chemotherapy, radiotherapy (other than a short cycle of palliative radiotherapy for bone pain), immunotherapy, or exposure to another investigational agent within 28 days (for biological agents decision on washout period will be made on a case by base basis) of first administration of the IMP:
- For nitrosoureas and mitomycin C within 6 weeks of first administration of NUC-7738
- For hormone therapy within 14 days of first administration of NUC-7738
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- Corticosteroid treatment is allowed during the screening period but should be weaned to a dose of 10 mg prednisolone (or steroids equivalent) by Cycle 1 Day 1.
- Prior toxicities from anti-cancer agents or radiotherapy, which have not regressed to Grade ≤1 severity (NCI-CTCAE v5.0), excluding neuropathy, ototoxicity and alopecia (which are excluded if ≥Grade 3).
- Presence of any uncontrolled concomitant illness, serious illness, medical conditions, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with their participation in the study, or with the interpretation of results, including the following:
- Congestive heart failure (New York Heart Association Class III or Class IV).
- Myocardial infarction within 6 months of the first dose of study medication.
- Unstable or poorly controlled angina pectoris.
- Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiogram finding.
- A history of or current risk factor for Torsades de Point (e.g., heart failure, hypokalaemia, or a family history of long QT syndrome).
- A history of, or current diagnosis of, interstitial pneumonitis or pulmonary fibrosis.
- Known human immunodeficiency virus positive or known active hepatitis B or C. Presence of an active bacterial or viral infection including Herpes zoster or chicken pox.
- Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location etc.) that, in the judgment of the Investigator, may affect the patient's ability to sign the informed consent and undergo study procedures.
- Currently pregnant, lactating or breastfeeding.
- QTc interval >450 milliseconds for males and >470 milliseconds for females.
- Concomitant use of drugs known to prolong QT/QTc interval.
- Concomitant use of strong CYP3A4 inducers or strong CYP3A4 inhibitors. The use of strong CYP3A4 inducers within 2 weeks of first receipt of study drug or the use of strong CYP3A4 inhibitors within 1 week of first receipt of study drug is also excluded.
- Have received a live vaccination within four weeks of first planned dose of study medication.
- NUC-7738 + pembrolizumab cohort only
- Any history of hypersensitivity or current contra-indication to the components of pembrolizumab (L-histidine, polysorbate 80, sucrose, sodium hydroxide, hydrochloric acid).
- Current contra-indication to immunotherapy with checkpoint inhibitors.
- Systemic steroid therapy or any immunosuppressive therapy (≥10 mg/day prednisone or equivalent).
- Known neutralising antibodies against checkpoint inhibitors.
- Patients previously exposed to checkpoint inhibitors who are not adequately treated for skin rash or have no replacement therapy for endocrinopathies.
- Any prior toxicity attributed to checkpoint inhibitors that resulted in discontinuation of therapy. These patients should be discussed on a case-by-case basis with the Medical Monitor.
- Active autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease or any condition that requires systemic steroids.
- Prior treatment with cell therapies.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
United Kingdom9 sites, 9 recruiting
- Recruiting
Cambridge University Hospitals NHS Foundation Trust (Addenbrookes Hospital)
Cambridge, CB2 0QQ
- Recruiting
Edinburgh Cancer Centre, Western General Hospital
Edinburgh, EH4 2XU
- Recruiting
The Beatson West of Scotland Cancer Centre
Glasgow, G12 0TN
- Recruiting
University College London Hospital
London, NW1 2PG
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
- Recruiting
Freeman Hospital
Newcastle, NE7 7DN
- Recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
- Recruiting
Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital
Preston, PR2 9HT
About this study
Official title: A Phase I/II, Open-label, Dose-escalation and Expansion Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-7738, a Nucleotide Analogue, in Patients With Advanced Solid Tumours and Lymphoma
This is a Phase I/II, dose-escalation and expansion study of NUC-7738 administered by intravenous infusion as a monotherapy and in combination with pembrolizumab.
In Phase I, NUC-7738 monotherapy is evaluated across two administration schedules (weekly or fortnightly) in a dose-escalation design in patients with advanced solid tumours. The main objectives are to assess the safety and tolerability of NUC-7738, in addition to establishing the Maximum Tolerated Dose (MTD) and dose administration schedule of NUC-7738 for further exploration in the Phase II part of the study.
In Phase II, the selected dose and designated dosing schedule will be further evaluated in dose-confirmation expansion cohorts enrolling a total of approximately 40 additional patients with advanced solid tumours. Based on emerging data, approximately 6 patients with cutaneous melanoma will be enrolled to these expansion cohorts and will receive NUC-7738 monotherapy. A further cohort will assess NUC-7738 in combination with pembrolizumab in approximately 6-12 patients with cutaneous melanoma. Based on efficacy signals observed in the initial melanoma combination cohort, a further expansion cohort will be initiated to expand to a total of 40 patients to allow a powered analysis. In addition, 12 patients with lymphoma (with potential expansion to a total of 25 patients) may be enrolled to receive NUC-7738 monotherapy.
- Conditions
- Advanced Cancer, Lymphoma, Solid Tumor, Melanoma
- Being tested
- NUC-7738, Pembrolizumab
- Keywords
- Solid tumors, Lymphoma, Cordycepin, Pembrolizumab, Melanoma
- Medical subject headings
- Lymphoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NUC-7738Drug
Also called Nucleotide Analogue
NUC-7738
PembrolizumabDrug
Also called Keytruda
Pembrolizumab
| Study group | Role | What they receive |
|---|---|---|
| NUC-7738 | Experimental | NUC-7738 administered by intravenous infusion on a weekly or fortnightly schedule. In the weekly dosing schedule, NUC-7738 is administered on Days 1 and 8 of a 14-day cycle. In the fortnightly dosing schedule, NUC-7738 is administered on Day 1 of a 14-day cycle. Receives: Drug: NUC-7738 |
| NUC-7738 + pembrolizumab | Experimental | NUC-7738 administered by intravenous infusion on a weekly schedule on Days 1, 8 and 15 of a 21-day cycle. Pembrolizumab administered by intravenous infusion every 3 weeks on Day 1 of a 21-day cycle. Receives: Drug: NUC-7738; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose-limiting toxicities
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with treatment-emergent adverse events (CTCAE v5.0)
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with clinically significant laboratory changes (CTCAE v5.0)
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with changes in physical exam, vital signs, and serial electrocardiograms.
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
MTD for NUC-7738 administered via weekly and fortnightly dosing schedules in patients with advanced solid tumours
Phase I
Measured: Until completion of Phase I (an average of 1 year)
Percentage change from baseline in tumour size
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007)
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Objective response rate (ORR)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the number of patients achieving a confirmed response (complete response [CR] or partial response [PR])
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Duration of response (DoR)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for CR or PR until the first date that recurrence or progressive disease (PD) is objectively documented (responders only)
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Disease control rate (DCR)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the proportion of patients achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Duration of stable disease (DoSD)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for SD until the first date that recurrence or PD is objectively documented
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Progression free survival (PFS)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from first dose of study treatment until the date of objective disease progression or death
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Secondary outcomes (21)
Phase I: Plasma concentration of NUC-7738 at end of infusion (Cinf)
Measured: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Maximum observed plasma concentration (Cmax) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Area under the plasma concentration-time curve (AUC) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Elimination half-life (t½) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase I: Volume of distribution of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase I: Clearance of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Plasma concentration of NUC-7738 at end of infusion (Cinf)
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Maximum observed plasma concentration (Cmax) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Area under the plasma concentration-time curve (AUC) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Elimination half-life (t½) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Volume of distribution of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Clearance of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Measured: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Percentage change from baseline in tumour size
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007)
The percentage change in the sum of longest diameters of target lesions from baseline to Week 8.
The best percentage change in the sum of longest diameters of target lesions from baseline to best on-treatment measurement
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
ORR
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007): defined as the number of patients achieving a confirmed response (complete response [CR] or partial response [PR])
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DoR
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for CR or PR until the first date that recurrence or progressive disease (PD) is objectively documented (responders only)
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DCR
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007): defined as the proportion of patients achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DoSD
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for SD until the first date that recurrence or PD is objectively documented
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
PFS
Phase I: Efficacy (per RECIST v 1.1 or Cheson et al, 2007): defined as the time from first dose of study treatment until the date of objective disease progression or death
Measured: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
Number of patients with treatment-emergent adverse events (CTCAE v5.0)
Phase II: Safety and tolerability of NUC-7738 as a single-agent or in combination with pembrolizumab in patients with advanced solid tumours and lymphoma
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with clinically significant laboratory changes (CTCAE v5.0)
Phase II: Safety and tolerability of NUC-7738 as a single-agent or in combination with pembrolizumab in patients with advanced solid tumours and lymphoma
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with changes in physical exam, vital signs, and serial electrocardiograms.
Phase II: Safety and tolerability of NUC-7738 as a single-agent or in combination with pembrolizumab in patients with advanced solid tumours and lymphoma
Measured: From the date of consent until 30 days after the last dose of NUC-7738 administered
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start17 Jun 2019
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NuCana plc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03829254
- Sponsor's protocol ID
- NuTide:701
- Other IDs
- 2018-003417-17, 2018
- Status last verified
- Jan 2026
- First submitted
- 30 Jan 2019
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-label, Dose-escalation and Expansion Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-7738, a Nucleotide Analogue, in Patients With Advanced Solid Tumours and Lymphoma
- ClinicalTrials.gov ID
- NCT03829254
- Acronym / sponsor ID
- NuTide:701
- Conditions
- Advanced Cancer, Lymphoma, Solid Tumor, Melanoma
- Keywords
- Solid tumors, Lymphoma, Cordycepin, Pembrolizumab, Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- NuCana plcUniversity, hospital or other
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 4 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I/II, dose-escalation and expansion study of NUC-7738 administered by intravenous infusion as a monotherapy and in combination with pembrolizumab.
In Phase I, NUC-7738 monotherapy is evaluated across two administration schedules (weekly or fortnightly) in a dose-escalation design in patients with advanced solid tumours. The main objectives are to assess the safety and tolerability of NUC-7738, in addition to establishing the Maximum Tolerated Dose (MTD) and dose administration schedule of NUC-7738 for further exploration in the Phase II part of the study.
In Phase II, the selected dose and designated dosing schedule will be further evaluated in dose-confirmation expansion cohorts enrolling a total of approximately 40 additional patients with advanced solid tumours. Based on emerging data, approximately 6 patients with cutaneous melanoma will be enrolled to these expansion cohorts and will receive NUC-7738 monotherapy. A further cohort will assess NUC-7738 in combination with pembrolizumab in approximately 6-12 patients with cutaneous melanoma. Based on efficacy signals observed in the initial melanoma combination cohort, a further expansion cohort will be initiated to expand to a total of 40 patients to allow a powered analysis. In addition, 12 patients with lymphoma (with potential expansion to a total of 25 patients) may be enrolled to receive NUC-7738 monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NUC-7738 | Experimental | Drug: NUC-7738NUC-7738 administered by intravenous infusion on a weekly or fortnightly schedule. In the weekly dosing schedule, NUC-7738 is administered on Days 1 and 8 of a 14-day cycle. In the fortnightly dosing schedule, NUC-7738 is administered on Day 1 of a 14-day cycle. |
| NUC-7738 + pembrolizumab | Experimental | Drug: NUC-7738, Drug: PembrolizumabNUC-7738 administered by intravenous infusion on a weekly schedule on Days 1, 8 and 15 of a 21-day cycle. Pembrolizumab administered by intravenous infusion every 3 weeks on Day 1 of a 21-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provision of signed written informed consent.
- Solid tumour cohorts only (Phase I and Phase II; excluding NUC-7738 + pembrolizumab cohort): Histologically confirmed diagnosis of an advanced solid tumour with measurable disease as per RECIST v1.1 criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions, which do not fulfil RECIST v1.1 criteria for measurable disease) for solid tumours.
- NUC-7738 + pembrolizumab cohort only (Phase II): Histologically confirmed diagnosis of metastatic cutaneous melanoma with measurable disease as per RECIST v1.1 criteria. Must have progressed on ≤2 prior lines of therapy for advanced/metastatic disease. In addition, patients may have been treated in the neoadjuvant/adjuvant setting. At least one prior line must have included a PD-1/PD-L1-containing regimen (either monotherapy or in combination) for which they progressed on.
- Lymphoma cohort only (Phase II): Relapsed refractory lymphoma (high grade and low grade B-NHL, Hodgkin's Lymphoma and T-cell lymphomas), which is not amenable to standard of care, is refractory to standard of care or for which no standard of care exists. Patients must have bi-dimensionally measurable disease as per Cheson et al, 2007 criteria for lymphoma.
- For solid tumours in single-agent Phase II cohorts only: patients should have received no more than 3 prior lines of treatment for metastatic disease.
Key exclusion criteria (31 listed)
- The following exclusion criteria apply to all patients. Please also refer to additional exclusion criteria for the NUC-7738 + pembrolizumab cohort below.
- History of allergic reaction fo any of the components of NUC-7738.
- Central nervous system or leptomeningeal metastases. Patients with brain metastases are eligible if they have no ongoing neurological symptoms, have not received corticosteroids within 7 days prior to enrolment, and show radiographic stability for at least 2 weeks.
- Chemotherapy, radiotherapy (other than a short cycle of palliative radiotherapy for bone pain), immunotherapy, or exposure to another investigational agent within 28 days (for biological agents decision on washout period will be made on a case by base basis) of first administration of the IMP:
- Prior toxicities from anti-cancer agents or radiotherapy, which have not regressed to Grade ≤1 severity (NCI-CTCAE v5.0), excluding neuropathy, ototoxicity and alopecia (which are excluded if ≥Grade 3).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NUC-7738Also: Nucleotide AnalogueNUC-7738 | Drug | NUC-7738, NUC-7738 + pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab | Drug | NUC-7738 + pembrolizumab |
Primary outcome
Number of patients with dose-limiting toxicities
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Number of patients with treatment-emergent adverse events (CTCAE v5.0)
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Number of patients with clinically significant laboratory changes (CTCAE v5.0)
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
Number of patients with changes in physical exam, vital signs, and serial electrocardiograms.
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Phase I: Safety and tolerability of NUC-7738 in patients with advanced solid tumours
MTD for NUC-7738 administered via weekly and fortnightly dosing schedules in patients with advanced solid tumours
Time frame: Until completion of Phase I (an average of 1 year)
Phase I
Percentage change from baseline in tumour size
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007)
Objective response rate (ORR)
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the number of patients achieving a confirmed response (complete response [CR] or partial response [PR])
Duration of response (DoR)
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for CR or PR until the first date that recurrence or progressive disease (PD) is objectively documented (responders only)
Disease control rate (DCR)
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the proportion of patients achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response
Duration of stable disease (DoSD)
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from the time measurement criteria are first met for SD until the first date that recurrence or PD is objectively documented
Progression free survival (PFS)
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days) in single-agent cohorts and Cycle 8 in combination cohorts (each cycle is 21 days), moving to every 12 weeks until the end of study (up to 22 months)
Phase II: Efficacy (per RECIST v 1.1, iRECIST or Cheson et al, 2007): defined as the time from first dose of study treatment until the date of objective disease progression or death
21 secondary outcomes
Phase I: Plasma concentration of NUC-7738 at end of infusion (Cinf)
Time frame: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Maximum observed plasma concentration (Cmax) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Area under the plasma concentration-time curve (AUC) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Samples collected on Days 1, 2, and 3 of Cycle 1 and Days 1 and 2 of Cycle 2 (cycle: 14 days).
Phase I: Elimination half-life (t½) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase I: Volume of distribution of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase I: Clearance of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Plasma concentration of NUC-7738 at end of infusion (Cinf)
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Maximum observed plasma concentration (Cmax) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Area under the plasma concentration-time curve (AUC) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Elimination half-life (t½) of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Volume of distribution of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Phase II: Clearance of NUC-7738, 3'-dA, 3'-deoxyinosine (3'-dI) and alanine phosphate metabolite of NUC-7738
Time frame: Single-agent cohorts: Samples collected on Days 1, 2 and 3 of each dose level (cycle: 14 days). Combination cohorts: Samples collected on Days 1, 2, and 3 of Cycle 1 and on Day 1 of the dose escalation step (cycle: 21 days)
Percentage change from baseline in tumour size
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
ORR
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DoR
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DCR
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
DoSD
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
PFS
Time frame: Assessed every 8 weeks following Day 1 up to and including Cycle 12 (each cycle is 14 days), moving to every 12 weeks until the end of study (up to 22 months)
Number of patients with treatment-emergent adverse events (CTCAE v5.0)
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with clinically significant laboratory changes (CTCAE v5.0)
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Number of patients with changes in physical exam, vital signs, and serial electrocardiograms.
Time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NUC-7738 and Pembrolizumab in people with Advanced Cancer and Lymphoma, run by NuCana plc at 9 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NuTide:701 Project Manager (+44 (0)131 357 1111, NuTide701@nucana.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with dose-limiting toxicities (time frame: From the date of consent until 30 days after the last dose of NUC-7738 administered). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.