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

NCT06380816 | Recruiting Phase 1

• 2 other identifiers: CRUKD/24/001ISRCTN26628699
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 2

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

Conditions

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

Keywords

HLA-G; Monoclonal Antibody; Cancer

Outcome Measures

Primary Outcomes (2)

• 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 \[module C\]).

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

• 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.

  From time of informed consent up to 12 months

Secondary Outcomes (7)

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

  From baseline radiological disease assessment up to 13 months.

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

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

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

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

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

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

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

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

Study Arms (2)

Module A (UCB4594 monotherapy dose escalation)

EXPERIMENTAL

Participants with advanced solid tumours from tumour types with known high levels of HLA-G expression (as reported in the literature) will be recruited.

Drug: UCB4594

Module B (UCB4594 monotherapy expansion)

EXPERIMENTAL

Participants with a specific tumour type where HLA-G expression is more prevalent may be recruited to receive UCB4594 monotherapy.

Drug: UCB4594

Interventions

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).

Module A (UCB4594 monotherapy dose escalation); Module B (UCB4594 monotherapy expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Have a negative serum pregnancy test within 7 days before enrolment and either:
• Agree to a form of highly effective contraception plus a barrier method, or
• 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:
• Agree to a barrier method of contraception or sexual abstinence
• Males with pregnant or breastfeeding partners must use barrier method contraception to prevent exposure of the foetus or neonate
• 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

Sponsors & Collaborators

• Cancer Research UK: lead
• UCB Biopharma SRL: collaborator

Study Sites (2)

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

NOT YET RECRUITING

Related Links

• Trial registration on ISRCTN

MeSH Terms

Conditions

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; Ovarian Neoplasms; Pancreatic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Esophageal Diseases; Stomach Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases

Study Officials

• Fiona Thistlethwaite, Prof

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fiona Thistlethwaite, Prof

CONTACT

+44 (0)161 9187672; fiona.thistlethwaite@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: April 24, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 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. Requests for individual deidentified participant data made within 5 years from the end of trial will be considered; requests made subsequently will be considered where possible.
• Access Criteria: 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.

Locations

GB (2)