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.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
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
Disqualifiers
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)
Trial design
Design model
Sequential
Treatments tested in this trial
UCB4594
Drug
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).
Treatment groups
167 Participants
are divided into 2 treatment groups
Group A: Module A (UCB4594 monotherapy dose escalation)Experimental treatment 1 intervention
Group B: Module B (UCB4594 monotherapy expansion)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
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 \[module C\]).
Time frame
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.
Time frame
From time of informed consent up to 12 months
Secondary outcomes
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).
Time frame
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.
Time frame
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.
Time frame
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.
Time frame
From Day 1 (date of first dose of UCB4594) up to 13 months.
Other outcomes
Sponsors and contacts
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