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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Malignant Solid Tumor, Oncology

Intervention / Treatment
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* Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A
* Diagnostic Test: Dynamic and Static - PET/CT scan
* Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part B
* Diagnostic Test: Static - PET/CT scan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Cohort 1 - 1 mg dose<br>1 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part A Cohort 2 - 2 mg dose<br>2 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part A Cohort 3 - 4 mg dose<br>4 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part A Cohort 4 - 8 mg dose<br>8 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part A Cohort 5 (optional) - 12 or 15 mg dose<br>12 or 15 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part A Cohort 6 - Optimal dose<br>Selected (optimal) mass dose as determined from results of Cohorts 1 through 5 of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part A<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Dynamic and Static - PET/CT scan<br>* 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.<br>|
| Experimental: Part B<br>Selected (optimal) dose of GEH200520 Injection from Part A with fixed dose of GEH200521 (18F) Injection administered together in 3 sequential repeat imaging visits | Drug: GEH200520 Injection / GEH200521 (18F) Injection - Part B<br>* Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush<br>Diagnostic Test: Static - PET/CT scan<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: The incidence of AEs upon causality to the IMPs. |  | 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. |  | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 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 (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. | The PK parameter to be assessed: AUC | 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. | The PK parameter to be assessed: Cmax | 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. | The PK parameter to be assessed: CL | 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. | The PK parameter to be assessed: V | 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. | The PK parameter to be assessed: t1/2 | 7 days | 
| Collection of the incidence, severity, changes between visits for AEs/SAEs/AESIs, for Part A subjects. | Incidence of AEs, SAEs, and Treatment-emergent AEs by system organ class and preferred term | 7 days | 
| Changes in physical examination status following administration of GEH200520 and GEH200521 (18F) for Part A subjects | The findings in the physical exam pre and post-administration will be summarized. | 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. | 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. | 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. | 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 | 
| Changes in heart rate as beats per minute following administration of GEH200520 and GEH200521 (18F) for Part A subjects | The occurrence of post-administration heart rate values outside the normal limits will be summarized. | Baseline, 2 hours, 24 hours, 7 days post IMP administration | 
| Changes in blood pressure in mmHg following administration of GEH200520 and GEH200521 (18F) for Part A subjects | The occurrence of post-administration blood pressure values outside the normal limits will be summarized. | Baseline, 2 hours, 24 hours, 7 days post IMP administration | 
| Changes in temperature as degree C following administration of GEH200520 and GEH200521 (18F) for Part A subjects | The occurrence of post-administration body temperature values outside the normal limits will be summarized. | Baseline, 2 hours, 24 hours, 7 days post IMP administration | 
| Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of GEH200520 and GEH200521 (18F) for Part A subjects | Descriptive statistics will be used to describe the observed values and change from baseline. | Baseline, 2 hours, 24 hours, 7 days post IMP administration | 
| 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/AESIs |  | 50 days | 
| 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 | 
| 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 physical examination status following administration of GEH200520 and GEH200521 (18F) for Part B subjects | The occurrence of post-administration physical exam status values outside the normal limits will be summarized. | Baseline, Day 15, Day 36, Day 50 | 
| Change from baseline in the results of serum biochemistry test results following administration of GEH200520 and GEH200521 (18F) for Part B subjects. | 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. | Baseline, Day 15, Day 36, Day 50 | 
| Change from baseline in the results of haematology test results following administration of GEH200520 and GEH200521 (18F) for Part B subjects. | 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. | Baseline, Day 15, Day 36, Day 50 | 
| Changes in heart rate as beats per minute following administration of GEH200520 and GEH200521 (18F) for Part B subjects | The occurrence of post-administration heart rate values outside the normal limits will be summarized. | Baseline, Day 15, Day 36, Day 50 | 
| Changes in blood pressure in mmHg following administration of GEH200520 and GEH200521 (18F) for Part B subjects | The occurrence of post-administration blood pressure values outside the normal limits will be summarized. | Baseline, Day 15, Day 36, Day 50 | 
| Changes in temperature as degree C following administration of GEH200520 and GEH200521 (18F) for Part B subjects | The occurrence of post-administration body temperature values outside the normal limits will be summarized. | Baseline, Day 15, Day 36, Day 50 | 
| Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of GEH200520 and GEH200521 (18F) for Part B subjects | Descriptive statistics will be used to describe the observed values and change from baseline. | Baseline, Day 15, Day 36, Day 50 | 
| 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. | The PK parameter to be assessed: AUC | 50 days | 
| 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. | The PK parameter to be assessed: Cmax | 50 days | 
| 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. | The PK parameter to be assessed: CL | 50 days | 
| 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. | The PK parameter to be assessed: V | 50 days | 
| 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. | The PK parameter to be assessed: t1/2 | 50 days | 
| 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 |