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

Phase 1
Recruiting
Conditions
Oncology
Malignant Solid Tumor
Interventions
Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A
Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part B
Diagnostic Test: Dynamic and Static - PET/CT scan
Diagnostic Test: Static - PET/CT scan
Registration Number
NCT05629689
Lead Sponsor
GE Healthcare
Brief Summary

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 . The estimated duration of Part B is approximately 64 days.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
Inclusion Criteria
  • 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 irresectable or metastatic solid tumour or a local and resectable head and neck squamous cell carcinoma.
  • Subject is eligible for ICI treatment.
  • Subject is male, or a female who agrees to comply with the protocol contraception method.
Exclusion Criteria
  • 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 any safety laboratory test results (clinical chemistry, haematology, and urinalysis) that, in the opinion of the Investigator, could compromise subject safety or protocol objectives.
  • Subject is pregnant or planning to become pregnant or is lactating.
  • Subject has a history of alcohol or drug abuse within the last year.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A Cohort 2 - 2 mg doseDynamic and Static - PET/CT scan2 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 5 (optional) - 12 or 15 mg doseGEH200520 Injection / GEH200521 (18F) Injection - Part A12 or 15 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 4 - 8 mg doseDynamic and Static - PET/CT scan8 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 6 - Optimal doseDynamic and Static - PET/CT scanSelected (optimal) mass dose as determined from results of Cohorts 1 through 5 of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 1 - 1 mg doseDynamic and Static - PET/CT scan1 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 3 - 4 mg doseGEH200520 Injection / GEH200521 (18F) Injection - Part A4 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 3 - 4 mg doseDynamic and Static - PET/CT scan4 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 6 - Optimal doseGEH200520 Injection / GEH200521 (18F) Injection - Part ASelected (optimal) mass dose as determined from results of Cohorts 1 through 5 of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 1 - 1 mg doseGEH200520 Injection / GEH200521 (18F) Injection - Part A1 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 2 - 2 mg doseGEH200520 Injection / GEH200521 (18F) Injection - Part A2 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part A Cohort 5 (optional) - 12 or 15 mg doseDynamic and Static - PET/CT scan12 or 15 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part BStatic - PET/CT scanSelected (optimal) dose of GEH200520 Injection from Part A with fixed dose of GEH200521 (18F) Injection administered together in 3 sequential repeat imaging visits
Part A Cohort 4 - 8 mg doseGEH200520 Injection / GEH200521 (18F) Injection - Part A8 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together
Part BGEH200520 Injection / GEH200521 (18F) Injection - Part BSelected (optimal) dose of GEH200520 Injection from Part A with fixed dose of GEH200521 (18F) Injection administered together in 3 sequential repeat imaging visits
Primary Outcome Measures
NameTimeMethod
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.Part A: 7 days
Part A: The incidence of AEs upon causality to the IMPs.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.Part B: 50 days
Secondary Outcome Measures
NameTimeMethod
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.7 days

The PK parameter to be assessed: CL

To assess the biodistribution and tumour uptake of GEH200521 (18F) Injection with the optimal GEH200520 Injection dose determined in Part A based on quantitative measurements of GEH200521 (18F) in regions of interest for Part B subjects.50 days
Changes in physical examination status following administration of GEH200520 and GEH200521 (18F) for Part B subjectsBaseline, Day 15, Day 36, Day 50

The occurrence of post-administration physical exam status values outside the normal limits will be summarized.

Change from baseline in the results of haematology test results following administration of GEH200520 and GEH200521 (18F) for Part B subjects.Baseline, Day 15, Day 36, Day 50

In this context, baseline is defined as the pre-treatment assessment at the screening visit. The occurrence of post injection values outside of normal limits and changes from baseline will be summarized.

To characterize the PK properties (V) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days

The PK parameter to be assessed: V

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.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.7 days

The PK parameter to be assessed: AUC

Collection of the incidence, severity, changes between visits for AEs/SAEs/AESIs, for Part A subjects.7 days

Incidence of AEs, SAEs, and Treatment-emergent AEs by system organ class and preferred term

Changes in physical examination status following administration of GEH200520 and GEH200521 (18F) for Part A subjectsBaseline, 24 hours, 7 days post IMP administration

The findings in the physical exam pre and post-administration will be summarized.

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.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.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.7 days

The PK parameter to be assessed: Cmax

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.7 days

The PK parameter to be assessed: V

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.7 days

The PK parameter to be assessed: t1/2

To assess the relationship between tumour GEH200521 (18F) Injection uptake (SUV value) and immune cell CD8+ expression score from a biopsy sample/resected lesion when available based on IHC results for Part B subjects.50 days
To compare changes in tumour GEH200521 (18F) Injection uptake with changes in computed tomography (CT) image assessment, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for Part B subjects when available .50 days
To compare changes in tumour GEH200521 (18F) Injection uptake with changes in computed tomography (CT) image assessment, according to [18F]-fluorodeoxyglucose (FDG) scans, when available for Part B subjects.50 days
Changes in blood pressure in mmHg following administration of GEH200520 and GEH200521 (18F) for Part B subjectsBaseline, Day 15, Day 36, Day 50

The occurrence of post-administration blood pressure values outside the normal limits will be summarized.

Changes in temperature as degree C following administration of GEH200520 and GEH200521 (18F) for Part B subjectsBaseline, Day 15, Day 36, Day 50

The occurrence of post-administration body temperature values outside the normal limits will be summarized.

To characterize the PK properties (AUC) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days

The PK parameter to be assessed: AUC

To compare immunogenicity, via the incidence of treatment-induced anti-drug antibodies responses, after multiple administrations of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days
Change from baseline in the results of serum biochemistry test results following administration of GEH200520 and GEH200521 (18F) for Part A subjects.Baseline, 24 hours, 7 days post IMP administration

In this context, baseline is defined as the pre-treatment assessment at the screening visit. The occurrence of post injection values outside of normal limits and changes from baseline will be summarized.

Changes in blood pressure in mmHg following administration of GEH200520 and GEH200521 (18F) for Part A subjectsBaseline, 2 hours, 24 hours, 7 days post IMP administration

The occurrence of post-administration blood pressure values outside the normal limits will be summarized.

To assess immunogenicity, via the incidence of treatment-induced anti-drug antibodies responses, after a single injection of the different GEH200520 Injection mass doses administered with a fixed dose of GEH200521 (18F) Injection for Part A subjects.7 days
Collection of the incidence, severity, changes between visits for AEs/SAEs/AESIs50 days
Change from baseline in the results of serum biochemistry test results following administration of GEH200520 and GEH200521 (18F) for Part B subjects.Baseline, Day 15, Day 36, Day 50

In this context, baseline is defined as the pre-treatment assessment at the screening visit. The occurrence of post injection values outside of normal limits and changes from baseline will be summarized.

Change from baseline in the results of haematology test results following administration of GEH200520 and GEH200521 (18F) for Part A subjects.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.

Changes in heart rate as beats per minute following administration of GEH200520 and GEH200521 (18F) for Part A subjectsBaseline, 2 hours, 24 hours, 7 days post IMP administration

The occurrence of post-administration heart rate values outside the normal limits will be summarized.

Changes in temperature as degree C following administration of GEH200520 and GEH200521 (18F) for Part A subjectsBaseline, 2 hours, 24 hours, 7 days post IMP administration

The occurrence of post-administration body temperature values outside the normal limits will be summarized.

Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of GEH200520 and GEH200521 (18F) for Part A subjectsBaseline, 2 hours, 24 hours, 7 days post IMP administration

Descriptive statistics will be used to describe the observed values and change from baseline.

Changes in heart rate as beats per minute following administration of GEH200520 and GEH200521 (18F) for Part B subjectsBaseline, Day 15, Day 36, Day 50

The occurrence of post-administration heart rate values outside the normal limits will be summarized.

Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of GEH200520 and GEH200521 (18F) for Part B subjectsBaseline, Day 15, Day 36, Day 50

Descriptive statistics will be used to describe the observed values and change from baseline.

To characterize the PK properties (Cmax) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days

The PK parameter to be assessed: Cmax

To characterize the PK properties (CL) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days

The PK parameter to be assessed: CL

To characterize the PK properties (t1/2) of total protein (GEH200520 and [18F]GEH200521 combined) following administration of GEH200520 Injection with GEH200521 (18F) Injection for Part B subjects.50 days

The PK parameter to be assessed: t1/2

Trial Locations

Locations (1)

UMC Groningen

🇳🇱

Groningen, Netherlands

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