Trial Title:
A Phase I/II Trial of UCB4594 in Participants With Advanced Cancer
NCT ID:
NCT06380816
Condition:
Advanced Solid Tumours
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Triple Negative Breast Neoplasms
Carcinoma, Renal Cell (Clear Cell Only)
Esophageal Neoplasms
Stomach Neoplasms (Excluding Gastrointestinal Stromal Tumors)
Uterine Cervical Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Conditions: Official terms:
Carcinoma
Neoplasms
Breast Neoplasms
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Gastrointestinal Stromal Tumors
Pancreatic Neoplasms
Ovarian Neoplasms
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck
Uterine Cervical Neoplasms
Triple Negative Breast Neoplasms
Conditions: Keywords:
HLA-G
Monoclonal Antibody
Cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
UCB4594
Description:
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).
Arm group label:
Module A (UCB4594 monotherapy dose escalation)
Arm group label:
Module B (UCB4594 monotherapy expansion)
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. 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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written (signed and dated) informed consent and capable of co-operating with
investigational medicinal product (IMP) administration and follow-up
2. 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
3. Measurable disease, according to RECIST v1.1
4. Life expectancy of at least 12 weeks
5. Eastern Cooperative Oncology Group performance status of 0 or 1
6. Haematological and biochemical indices within defined ranges. These measurements
should be performed to confirm the patient's eligibility to participate in the trial
7. 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
Exclusion Criteria:
1. 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
2. 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)
3. 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
4. Pregnant or breastfeeding female patients (or planning to breastfeed)
5. 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:
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
6. 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
7. Surgery from which the patient has not yet recovered
8. 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
9. Known to be serologically positive for hepatitis B virus, hepatitis C virus or human
immunodeficiency virus
10. 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
11. 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
12. Hypersensitivity to the ingredients/excipients (including polysorbate 80) in UCB4594
13. 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)
14. History of Grade ≥3 infusion-related reaction to monoclonal antibodies or similar
drugs
15. Prior treatment with HLA-G, immunoglobulin-like transcript (ILT)2 or ILT4-targeting
drug
16. Live, attenuated vaccine within 28 days prior to the first dose of IMP
17. Increased risk due to tumour flare (e.g., an initial increase in tumour size that
may lead to obstruction of airways, etc)
18. 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
19. Evidence of bleeding diathesis
20. 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
21. Participant in or plans to join another interventional trial
22. Other current malignancies. Cancer survivors who have undergone potentially curative
therapy for prior malignancy with no evidence of disease for 3+ years are eligible
23. Any other condition that, in the Investigator's opinion, means the trial is not in
the patient's best interest
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Fiona Thistlethwaite, Prof
Phone:
+44 (0)161 9187672
Email:
fiona.thistlethwaite@nhs.net
Facility:
Name:
University Hospital Southampton NHS Foundation Trust
Address:
City:
Southampton
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Ioannis Karydis, Prof
Email:
I.Karydis@soton.ac.uk
Start date:
July 9, 2024
Completion date:
November 2029
Lead sponsor:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
UCB Biopharma SRL
Agency class:
Industry
Source:
Cancer Research UK
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06380816
https://www.isrctn.com/ISRCTN26628699
