A Study to Evaluate GEH200520/GEH200521 (18F) Safety and Tolerability When Used for PET Scans in Patients With Solid Tumour Malignancies

Официальное название

A Phase 1a/1b, Multi-Centre, Open-Label, Dose-Escalation and Dose-Expansion Study in Patients With Solid Tumour Malignancies to Evaluate GEH200520 Injection / GEH200521 (18F) Injection Safety and Tolerability, PET Imaging, Pharmacokinetics, and Changes in Imaging After Treatment

Обзор

Part A: The purpose of this part is to assess the safety of GEH200520 and GEH200521 (18F) when administered to patients with solid cancer. Subjects will be requested to complete 3 study visits: 1 screening visit, 1 imaging visit (over 24 hours) and 1 follow-up visit (7 days later). The estimated duration of Part A is 21 days. Part B: The purpose of this part of the study is to assess the imaging quality and findings as well as the safety and tolerability of GEH200520 and GEH200521 (18F) when administered to patients with cancer before and after immunotherapy treatment. Subjects will be requested to complete 7 study visits: 1 screening visit, the first imaging visit, followed by 2 immunotherapy immune-checkpoint inhibitor (ICI) treatment visits and 2 additional imaging and 1 follow-up visit. Two late imaging transfer expected post follow up visit. The estimated duration for subject participation in Part B is approximately 64 days.

Вмешательства

• Препарат GEH200520 Injection / GEH200521 (18F) Injection - Part A
  Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush
• Диагностический тест Dynamic and Static - PET/CT scan
  Dynamic whole-body PET/CT scan starting at the time of injection (sequential scans over 90 minutes anticipated) followed by static whole-body scans starting at 150 minutes, 270 minutes, and (optional) 24 hours after injection.
• Препарат GEH200520 Injection / GEH200521 (18F) Injection - Part B
  Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush
• Диагностический тест Static - PET/CT scan
  Whole-body PET/CT scan (up to 30 min). Exact timing will be determined from Part A. An optional dynamic scan may be acquired in addition to the required whole-body PET/CT scan at each imaging visit.

Первичные конечные точки

• Part A: The incidence of AEs upon causality to the IMPs. [Срок оценки: Part A: 7 days]
• Part A: The severity of AEs per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) upon causality to the IMPs. [Срок оценки: Part A: 7 days]
• To evaluate the time-course changes in GEH200521 (18F) Injection uptake after immune-checkpoint inhibitor (ICI) treatment cycles compared to baseline. [Срок оценки: Part B: 50 days]

Вторичные конечные точки (12)

• To evaluate the radiation dosimetry of a fixed dose of GEH200521 (18F) Injection when administered with the different GEH200520 Injection mass doses by cumulated activity in source regions and by entire body. [Срок оценки: 7 days]
• To evaluate the optimal imaging time window for GEH200521 (18F) Injection positron emission tomography (PET) imaging when administered with different GEH200520 Injection mass doses for Part A subjects. [Срок оценки: 7 days]
• To determine the appropriate mass dose of GEH200520 Injection for administration with GEH200521 (18F) Injection to achieve an acceptable PET image quality for Part A subjects. [Срок оценки: 7 days]
• To characterize the pharmacokinetic (PK) properties (AUC) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of different GEH200520 Injection mass doses with a fixed dose of GEH200521 (18F) Injection for Part A subjects. [Срок оценки: 7 days]
• To characterize the pharmacokinetic (PK) properties (Cmax) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of different GEH200520 Injection mass doses with a fixed dose of GEH200521 (18F) Injection for Part A subjects. [Срок оценки: 7 days]
• To characterize the pharmacokinetic (PK) properties (CL) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of different GEH200520 Injection mass doses with a fixed dose of GEH200521 (18F) Injection for Part A subjects. [Срок оценки: 7 days]
• To characterize the pharmacokinetic (PK) properties (V) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of different GEH200520 Injection mass doses with a fixed dose of GEH200521 (18F) Injection for Part A subjects. [Срок оценки: 7 days]
• To characterize the pharmacokinetic (PK) properties (t1/2) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of different GEH200520 Injection mass doses with a fixed dose of GEH200521 (18F) Injection for Part A subjects. [Срок оценки: 7 days]
• Collection of the incidence, severity, changes between visits for AEs/SAEs/AESIs, for Part A subjects. [Срок оценки: 7 days]
• Changes in physical examination status following administration of GEH200520 and GEH200521 (18F) for Part A subjects [Срок оценки: Baseline, 24 hours, 7 days post IMP administration]
• Change from baseline in the results of serum biochemistry test results following administration of GEH200520 and GEH200521 (18F) for Part A subjects. [Срок оценки: Baseline, 24 hours, 7 days post IMP administration]
• Change from baseline in the results of haematology test results following administration of GEH200520 and GEH200521 (18F) for Part A subjects. [Срок оценки: Baseline, 24 hours, 7 days post IMP administration]

Критерии участия

Критерии включения

• The subject is able and willing to comply with all study procedures as described in the protocol, including the imaging day pre-visit requirements, and has read, signed, and dated an informed consent form prior to any study procedures being performed.
• The subject is male or female, ≥18 years of age.
• Subject has a life expectancy ≥12 weeks.
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Subject has an unresectable or metastatic solid tumour or a local and resectable head and neck squamous cell carcinoma, or an unresectable stage III-IV melanoma.
• Subject is eligible for ICI treatment per Investigator judgement.
• Subject has at least 1 measurable tumour lesion documented on CT/magnetic resonance imaging (MRI) RECIST v1.1 during the last 12 months.
• Subject has a tumour lesion(s) of which a biopsy can safely be obtained according to standard clinical care procedures.
• Subject is male or female that agrees to adhere to the protocol contraception methods.

Критерии исключения

• Subject is unable to undergo all procedures in the study and/or is unable to remain still and tolerate the imaging procedure.
• Subject has 12-lead ECG significant findings during screening, per Investigator's assessment.
• Subject is not stable due to medical condition or therapy that, in the opinion of the Investigator, could compromise subject safety or protocol objectives.
• Subject has active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
• Subject has serious non-malignant disease or conditions that, in the opinion of the Investigator, could compromise subject safety or protocol objectives.
• Subject has B or T cell lymphoma.
• Subject has brain or bone-marrow metastasis that, in the opinion of the Investigator, could compromise subject safety or protocol objectives.
• Subject has signs or symptoms of systemic infection within 2 weeks prior to imaging day.
• Subject has history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins or known allergy to the study IMP ingredients and/or the proposed ICI therapy.
• Subject has any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the ICI treatment, or that may affect the interpretation of the results or render the subject at high risk from complications.
• Subject has laboratory values out of range per protocol.
• Subject has any safety laboratory test results (blood chemistry, haematology, and urinalysis) that, in the opinion of the Investigator, could compromise subject safety or protocol objectives.
• Subject has had any major surgery within 4 weeks prior to enrollment.
• Subject has been enrolled in another interventional clinical study within the 30 days before screening for this study, except for the study site IIS.
• Subject is pregnant or planning to become pregnant or is breastfeeding.
• Subject has a history of alcohol or drug abuse within the last year.
• Subject has had treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to dosing with the IMP.
• Subject has had treatment with systemic immunosuppressive medications within 2 weeks prior to dosing with the IMP.
• Subject has received acute, low-dose, systemic immunosuppressant medications that, in the opinion of the Investigator, could compromise protocol objectives.
• Subject has used systemic corticosteroids to treat inflammatory or autoimmune symptoms.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Нидерланды · 2 центра

• Amsterdam UMC — Amsterdam
• UMC Groningen — Groningen

Идентификаторы

NCT: NCT05629689 · GE-269-001 · 2024-515218-42-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗