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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Oncology; Malignant Solid Tumor
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yaron Raiter, MD; Phone Number: +31 6 21288463; Email: yaron.raiter@ge.com
• Study Contact Backup: Name: Jane Bateman, RN; Phone Number: (508) 5730016; Email: Jane.Bateman@ge.com

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • UMC Groningen
    • Contact: Derk Jan de Groot, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Cohort 1 - 1 mg dose; 1 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together	Drug: 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; Diagnostic test: 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.
Experimental: Part A Cohort 2 - 2 mg dose; 2 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together	Drug: 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; Diagnostic test: 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.
Experimental: Part A Cohort 3 - 4 mg dose; 4 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together	Drug: 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; Diagnostic test: 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.
Experimental: Part A Cohort 4 - 8 mg dose; 8 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together	Drug: 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; Diagnostic test: 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.
Experimental: Part A Cohort 5 (optional) - 12 or 15 mg dose; 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; Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush; Diagnostic test: 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.
Experimental: Part A Cohort 6 - Optimal dose; 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; Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush; Diagnostic test: 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.
Experimental: Part B; 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; Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush; Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: GE Healthcare
• Investigators: Study Director: Yaron Raiter, MD, GE Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GE-269-001; 2022-000246-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No