Actively Recruiting

Phase 1
Phase 2
Age: 18Years +
All Genders
NCT03829254

A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma

Led by NuCana plc · Updated on 2026-01-12

135

Participants Needed

9

Research Sites

371 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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

Official Title

A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed written informed consent is provided.
  • Histologically confirmed advanced solid tumor with measurable or evaluable disease for solid tumor cohorts (Phase I and II, excluding combination cohort).
  • Metastatic cutaneous melanoma with measurable disease and progression on at least two prior therapies, including PD-1/PD-L1 regimen for combination cohort (Phase II).
  • Relapsed refractory lymphoma not amenable or refractory to standard care with measurable disease for lymphoma cohort (Phase II).
  • No more than three prior treatments for metastatic disease in single-agent Phase II solid tumor cohorts.
  • Age 18 years or older with no upper age limit.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Adequate bone marrow, liver, and kidney function.
  • Ability to follow study requirements.
  • Female patients of childbearing potential must have a negative pregnancy test within 3 days before first NUC-7738 dose.
  • Agreement to practice abstinence or use two contraception methods from screening until 6 months after last study dose.
  • Willingness to undergo tumor biopsies at screening and during therapy unless clinically unsafe.
  • Advised to avoid or minimize skin and eye exposure to UV light during study and for 4 weeks after last dose.
Not Eligible

You will not qualify if you...

  • History of allergic reactions to components of NUC-7738.
  • Presence of central nervous system or leptomeningeal metastases, except stable brain metastases without symptoms or recent corticosteroids.
  • Recent chemotherapy, radiotherapy (except short palliative), immunotherapy, or other investigational agents within specified washout periods.
  • Unresolved toxicities from previous anti-cancer treatments above Grade 1 severity (with some exceptions).
  • Uncontrolled or serious illnesses including severe heart failure, recent heart attack, unstable angina, significant ECG abnormalities, risk factors for Torsades de Point, interstitial lung disease or fibrosis.
  • Known HIV positive or active hepatitis B or C infection, or active bacterial/viral infections.
  • Conditions impairing ability to consent or participate.
  • Pregnancy, lactation, or breastfeeding.
  • QTc interval above specified thresholds.
  • Use of drugs prolonging QT/QTc interval or strong CYP3A4 inducers/inhibitors within specified time frames.
  • Live vaccination within 4 weeks before first study dose.
  • For combination cohort: hypersensitivity to pembrolizumab components, contraindications to immunotherapy, systemic steroid or immunosuppressive therapy, known neutralizing antibodies to checkpoint inhibitors, unresolved toxicities from checkpoint inhibitors, active or history of autoimmune disease, or prior cell therapy treatments.

AI-Screening

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Trial Site Locations

Total: 9 locations

1

Cambridge University Hospitals NHS Foundation Trust (Addenbrookes Hospital)

Cambridge, United Kingdom, CB2 0QQ

Actively Recruiting

2

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, United Kingdom, EH4 2XU

Actively Recruiting

3

The Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0TN

Actively Recruiting

4

University College London Hospital

London, United Kingdom, NW1 2PG

Actively Recruiting

5

The Royal Marsden NHS Foundation Trust

London, United Kingdom, SW3 6JJ

Actively Recruiting

6

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Actively Recruiting

7

Freeman Hospital

Newcastle, United Kingdom, NE7 7DN

Actively Recruiting

8

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom, OX3 9DU

Actively Recruiting

9

Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital

Preston, United Kingdom, PR2 9HT

Actively Recruiting

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Research Team

N

NuTide:701 Project Manager

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

2

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