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Advanced Solid TumoursPhase 1/2NCT06380816

A Phase I/II Trial of UCB4594 in Participants With Advanced Cancer

A Phase 1/2 study testing UCB4594 in people with Advanced Solid Tumours and Squamous Cell Carcinoma of Head and Neck, run by Cancer Research UK at 4 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This clinical trial is looking at UCB4594. This is the first time the drug is being tested in humans. UCB4594 is a type of drug called a monoclonal antibody. It has been designed to work by targeting a protein called human leucocyte antigen G (HLA-G) that is found in high levels on some cancer cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
UCB4594
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
167 participants
Where
4 sitesUnited Kingdom
Study dates
9 Jul 2024to Nov 2029
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

  • Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product (IMP) administration and follow-up
  • Participant population: Histologically or cytologically proven advanced solid tumours (as specified below), refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the participant. Module A (dose escalation): Tumour types which have shown high levels of human HLA-G expression (as reported in the literature): head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer, triple-negative breast cancer, renal cell cancer (clear cell only), oesophago-gastric cancer (excluding gastrointestinal stromal tumour), cervical cancer, ovarian cancer, pancreatic cancer. N.B. Participants with small cell type cancers on histology/cytology are excluded. Pre-treatment biopsies are mandatory for all participants. Paired biopsies will be mandatory for participants from doses of 30 mg and higher. Participants must have disease amenable to biopsy (excluding bone metastases) as deemed safe by the Investigator
  • Measurable disease, according to RECIST v1.1
  • Life expectancy of at least 12 weeks
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Haematological and biochemical indices within defined ranges. These measurements should be performed to confirm the patient's eligibility to participate in the trial
  • Aged 18 years or over at the time consent is given. Participants aged 16-17 years may be eligible for recruitment to the backfill cohorts in dose escalation once adequate safety and toxicity data have been established in participants aged 18 years or over. All relevant data will be reviewed and a decision on the inclusion of participants aged 16-17 years will be made by the Trial Management Group

Who cannot join

  • Radiotherapy (except palliative), endocrine therapy (unless for non-malignant disease), chemotherapy, targeted therapy or immunotherapy, or any other IMPs during the previous 4 weeks or 5 half-lives (whichever is shorter) before the first dose of IMP
  • Ongoing toxicity of previous treatments >CTCAE Grade 1 (except alopecia of any grade, stable Grade 2 peripheral neuropathy or hormone-replacement therapy (HRT)-managed endocrine disorders)
  • Patients with rapidly progressing / symptomatically deteriorating brain/leptomeningeal metastases/untreated brain metastases are excluded. Patients with previously treated brain metastases are eligible if they haven't had a seizure or a clinically significant change in neurological status or required steroids in the last 2 weeks
  • Pregnant or breastfeeding female patients (or planning to breastfeed)
  • Women of childbearing potential. However, those not already pregnant or breastfeeding (or who discontinue breastfeeding) and meet the following are eligible:
  • 5.1. Have a negative serum pregnancy test within 7 days before enrolment and either:
Show all 34Show fewer
  • 5.2.1. Agree to a form of highly effective contraception plus a barrier method, or
  • 5.2.2. Agree to sexual abstinence
  • Effective from the negative pregnancy test, throughout the trial and for 10 months after the last dose of UCB4594
  • Male patients with partners of childbearing potential. However, patients who meet the following are eligible:
  • 6.1. Agree to a barrier method of contraception or sexual abstinence
  • 6.2. Males with pregnant or breastfeeding partners must use barrier method contraception to prevent exposure of the foetus or neonate
  • 6.3. Non-vasectomised males must also ensure any partner of childbearing potential uses highly effective contraception or agrees to sexual abstinence
  • Effective from the date of the first dose of UCB4594, throughout the trial and for 5 months after the last dose of UCB4594 N.B. Males must refrain from donating sperm for the same period
  • Surgery from which the patient has not yet recovered
  • High medical risk because of non-malignant systemic disease, including serious or uncontrolled infection (requiring intravenous antibiotics) or unexplained fever >38°C within 2 weeks prior to the first dose of UCB4594
  • Known to be serologically positive for hepatitis B virus, hepatitis C virus or human immunodeficiency virus
  • Active or suspected autoimmune disease, or any history of autoimmune condition that required systemic corticosteroids or immunosuppressive agents. Patients who have ever had a transplant are excluded. This does not apply to patients with: vitiligo, alopecia, or type I diabetes mellitus, psoriasis not requiring chronic systemic immunosuppressive treatment within the past 2 years, stable autoimmune-mediated hypothyroidism on HRT, and Raynaud's syndrome
  • Are being treated with escalating or supraphysiologic doses of corticosteroids or immunosuppressive agents. Participants with immunotherapy-related hypophysitis adequately treated with physiologic doses of steroids are not excluded. Use of topical, ophthalmic, inhaled, intermittent steroid injections, and intranasal corticosteroids are permitted
  • Hypersensitivity to the ingredients/excipients (including polysorbate 80) in UCB4594
  • History of significant toxicities from treatment of immune checkpoint inhibitors (CPIs) that necessitated permanent discontinuation (Patients who started on combination CPI [e.g., ipilimumab/nivolumab] and had toxicity requiring discontinuation of one CPI [e.g., continued with nivolumab single agent] are not excluded)
  • History of Grade ≥3 infusion-related reaction to monoclonal antibodies or similar drugs
  • Prior treatment with HLA-G, immunoglobulin-like transcript (ILT)2 or ILT4-targeting drug
  • Live, attenuated vaccine within 28 days prior to the first dose of IMP
  • Increased risk due to tumour flare (e.g., an initial increase in tumour size that may lead to obstruction of airways, etc)
  • Significant active pulmonary disease or condition at screening, including:
  • 18.1. Lymphangitis carcinomatosa
  • 18.2. History of interstitial lung disease or pulmonary fibrosis
  • 18.3. History of pulmonary inflammatory disease
  • Evidence of bleeding diathesis
  • Significant cardiovascular disease, defined as a history of: congestive heart failure requiring therapy or left ventricular ejection fraction <40%, unstable angina pectoris or myocardial infarction within 6 months prior to entry, or current poorly controlled angina (symptoms weekly or more), clinically significant cardiac arrhythmia within 6 months prior to entry (asymptomatic atrial fibrillation or asymptomatic first-degree heart block permitted), or myocarditis. Presence of symptomatic or severe valvular heart disease. Baseline QT interval corrected by Fridericia >450 msec for males and >470 msec for females on triplicate electrocardiogram is ineligible
  • Participant in or plans to join another interventional trial
  • Other current malignancies. Cancer survivors who have undergone potentially curative therapy for prior malignancy with no evidence of disease for 3+ years are eligible
  • Any other condition that, in the Investigator's opinion, means the trial is not in the patient's best interest

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Fiona Thistlethwaite, Prof contact

+44 (0)161 9187672

the-christie.ecmt.enquiries@nhs.net

United Kingdom4 sites, 4 recruiting

  • Guy's Hopsital

    London, SE1 9RT

    James Spicer, Dr, +44 (0)20 7188 4260, James.Spicer@kcl.ac.uk

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester

    Fiona Thistlethwaite, Prof, +44 (0)161 9187672, the-christie.ecmt.enquiries@nhs.net

    Recruiting

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne, NE7 7DN

    Christoph Oing, Dr, +44 (0)191 213 8476, c.oing@nhs.net

    Recruiting

  • University Hospital Southampton NHS Foundation Trust

    Southampton

    Ioannis Karydis, Prof, I.Karydis@soton.ac.uk

    Not yet recruiting

Other trials in United Kingdom

About this study

Official title: A Cancer Research UK Phase I/II Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of UCB4594 Alone and in Combination With Anti-cancer Treatments in Participants With Advanced Malignancies

This clinical trial is looking at UCB4594. This is the first time the drug is being tested in humans. UCB4594 is a type of drug called a monoclonal antibody. It has been designed to work by targeting a protein called human leucocyte antigen G (HLA-G) that is found in high levels on some cancer cells. By attaching itself to this protein it may help the immune system to attack and kill the cancer cells.

The four main aims of the clinical trial are to find out:

  1. The best dose of UCB4594 that can be given safely to participants in the trial.
  2. What the side effects of UCB4594 are and how they can be managed.
  3. What happens to UCB4594 inside the body and how it affects cancer cells.
  4. Whether UCB4594 can cause cancer to shrink.
Read the detailed description

What does the study involve?

This clinical trial is split into two phases.

Phase I (Module A) is the 'dose escalation' phase. This is where small groups of participants receive UCB4594 at a certain dose level starting with a low dose level. After reviewing the results obtained at each dose level, it will be decided whether or how much to increase the dose for the next group of participants. This part of the study aims to find the best dose to give that does not cause too many side effects.

Phase II is the 'dose expansion' phase. This starts when the dose escalation phase has worked out the best dose of UCB4594 to give. In this part of the trial UCB4594 will be given alone (Module B) or in combination with other anti-cancer drugs (Module C). This will allow us to find out more about how the drug is working and whether UCB4594 affects cancer. Details for Module C of the dose expansion phase will be added when the types of cancer and anti-cancer drugs are defined.

What are the possible benefits and risks of participating?

UCB4594 is a new drug that has never been given to humans before. Possible risks and benefits are based on laboratory tests and experience with similar drugs but there is not yet any information about the effects of UCB4594 in humans. Participants in the trial will be monitored closely to find out the effects of UCB4594.

Being tested
UCB4594
Keywords
HLA-G, Monoclonal Antibody, Cancer
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Triple Negative Breast Neoplasms, Carcinoma, Esophageal Neoplasms, Stomach Neoplasms, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UCB4594Drug

    Participants will receive UCB4594 as an intravenous infusion once every 3 weeks for up to 18 cycles, with each cycle lasting 21 days (~1 year).

Study groups in NCT06380816
Study groupRoleWhat they receive
Module A (UCB4594 monotherapy dose escalation)ExperimentalParticipants with advanced solid tumours from tumour types with known high levels of HLA-G expression (as reported in the literature) will be recruited.
Receives: Drug: UCB4594
Module B (UCB4594 monotherapy expansion)ExperimentalParticipants with a specific tumour type where HLA-G expression is more prevalent may be recruited to receive UCB4594 monotherapy.
Receives: Drug: UCB4594

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 dose (RP2D) of UCB4594

    The RP2D will be the dose(s) of UCB4594 (in units of mg) selected for further evaluation and will be determined based on the maximum tolerated dose or maximum administered dose (MTD/MAD) and all available safety, efficacy, pharmacokinetic (PK) and pharmacodynamic data (all modules - dose escalation [module A], monotherapy dose expansion [module B] and any combination modules [module C]).

    Measured: From Day 1 (date of first dose of UCB4594) up to Day 21.

  2. Frequency of adverse events (AEs) considered at least possibly related to UCB4594 (up to 18 cycles).

    AE data will be collected for UCB4594 (all modules) and/or other anti-cancer treatments (Module C), and the number of Grade 3, 4 and 5 AEs at least possibly related to UCB4594 (all modules) and/or other anti-cancer treatments (Module C) for up to 18 cycles (~12 months) of dosing determined. AEs, including relatedness, seriousness and severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, will be assessed by the Investigator.

    Measured: From time of informed consent up to 12 months

Secondary outcomes (8)

  1. Number of patients achieving a complete response (CR)/immune CR (iCR) or partial response (PR)/immune PR (iPR) to UCB4594 (all modules).

    Number of patients achieving a CR/iCR or PR/iPR to UCB4594 (all modules) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and immune RECIST (iRECIST).

    Measured: From baseline radiological disease assessment up to 13 months.

  2. Maximum concentration of UCB4594 (monotherapy modules; Modules A and B).

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  3. Minimum concentration of UCB4594 (monotherapy modules; Modules A and B).

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  4. Area under the curve of UCB4594 (monotherapy modules; Modules A and B).

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  5. Steady state volume of distribution of UCB4594 (monotherapy modules; Modules A and B).

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  6. Clearance of UCB4594 (monotherapy modules; Modules A and B).

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  7. Terminal elimination half-life of UCB4594 (Monotherapy modules; Modules A and B)

    UCB4594 concentrations will be measured in serum.

    Measured: From Day 1 (date of first dose of UCB4594) up to 13 months.

  8. Frequency of AEs considered at least possibly related to UCB4594 (up to end of AE reporting period).

    The frequency of AEs will be assessed for UCB4594 (all modules) and/or other anti-cancer treatments (Module C), and the number of Grade 3, 4 and 5 AEs at least possibly related to UCB4594 (all modules) and/or other anti-cancer treatments (Module C) determined. AEs, including relatedness, seriousness and severity according to NCI CTCAE Version 5.0, will be assessed by the Investigator.

    Measured: AEs are collected from the date of informed consent until 6 months after the last dose of UCB4594.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2024
  2. Study start9 Jul 2024
  3. Primary completionNov 2029 (estimated)
  4. Study completionNov 2029 (estimated)

Resources

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
167 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06380816
Sponsor's protocol ID
CRUKD/24/001
Other IDs
ISRCTN26628699
Status last verified
May 2026
First submitted
27 Mar 2024
Last updated
8 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data from this trial and the final clinical study protocol will be submitted to a public registry and will be available immediately following publication, with no end date. Individual deidentified participant data that underlie the results reported will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor. All requests made within 5 years from the end of trial will be considered; requests made subsequently will be considered where possible. Requests should be submitted to drugdev@cancer.org.uk.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing UCB4594 in people with Advanced Solid Tumours and Squamous Cell Carcinoma of Head and Neck, run by Cancer Research UK at 4 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 7 inclusion and 34 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 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 Fiona Thistlethwaite, Prof (+44 (0)161 9187672, the-christie.ecmt.enquiries@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 dose (RP2D) of UCB4594 (time frame: From Day 1 (date of first dose of UCB4594) up to Day 21.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06380816.

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 8 May 2026.

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