Advanced solid tumours Cancer
Conditions
Interventions
Dose escalation phase: Participants will receive UCB4594 as an intravenous infusion once every 3 weeks. The dose administered will be between 3 mg and 1600 mg.
Expansion phase: Participants will rec
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Written (signed and dated) informed consent and capable of co-operating with 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 leucocyte antigen (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
Exclusion criteria: 1. Radiotherapy (except palliative), endocrine therapy (unless for non-malignant disease), chemotherapy, targeted therapy or immunotherapy, or any other investigational medicinal products (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 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 IV 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/nivol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The recommended Phase 2 dose (RP2D) of UCB4594 will be determined both for UCB4594 on its own and with other anti-cancer drugs, 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]). Evaluation of this endpoint will occur once all patients in each module (Module A, B or C) have completed the dose-limiting toxicity (DLT) assessment period (21 days) and all relevant data has been collected. 2. The frequency of adverse events (AEs) considered at least possibly related to UCB4594. AE data will be collected for UCB4594 (all modules) and in combination with 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 with 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. Evaluation of this endpoint will occur once the last patient recruited overall has received up to 18 cycles (~12 months) of UCB4594. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcomes: 1. Tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and immune RECIST (iRECIST) (all modules) and Overall Response Rate (ORR) (expansion phase; Modules B and C). ORR is defined as the proportion of participants who achieve complete response (CR/iCR) or partial response (PR/iPR) as the best overall response according to RECIST v1.1 and iRECIST. Response will be assessed at baseline, once every 6–9 weeks, and at End of Treatment. 2. The PK parameters of UCB4594 (including maximum concentration, minimum concentration, area under the curve, steady state volume of distribution, clearance, and terminal elimination half-life) (monotherapy modules; Modules A and B). UCB4594 concentrations will be measured in serum in samples collected from participants at up to 18 timepoints during Cycles 1 to 2, two timepoints for every subsequent cycle, and at the End of Treatment Visit for Module A (dose escalation); 2 samples will be taken for every cycle, and a further sample at the End of Treatment Visit for Module B (monotherapy expansion). 3. The frequency of AEs considered at least possibly related to UCB4594. The frequency of AEs will be assessed for UCB4594 (all modules) and/or with 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. AEs are collected from the date of informed consent until 6 months after the last dose of UCB4594. Previous key secondary outcomes: 1. Tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and immune RECIST (iRECIST) (all modules) and Overall Response Rate (ORR) (expansion phase; Modules B and C). ORR is defined as the proportion of participants who achieve complete response (CR/iCR) | — |
Countries
England, United Kingdom
Outcome results
None listed