En undersøgelse til evaluering af GEH200520/GEH200521 (18F) sikkerhed og tolerabilitet ved brug til PET-scanninger hos patienter med solid tumor malignitet
Et fase 1a/1b, multicenter, åbent label, dosis-eskalering og dosisudvidelsesundersøgelse i patienter med solide tumorer til evaluering af GEH200520-injektion / GEH200521 (18F) Injektionssikkerhed og -tolerabilitet, PET-billeddannelse, og farmakokinetik Billeddannelse efter behandling
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
-
Amsterdam, Holland
- Amsterdam UMC
-
Groningen, Holland
- UMC Groningen
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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 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.
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 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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Diagnostisk
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Part A Cohort 1 - 1 mg dose
1 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: Part A Cohort 2 - 2 mg dose
2 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: Part A Cohort 3 - 4 mg dose
4 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: Part A Cohort 4 - 8 mg dose
8 mg mass dose of GEH200520 Injection with fixed dose of GEH200521 (18F) Injection administered together |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: 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 |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: 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 |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
|
Eksperimentel: 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 |
Administration of GEH200520 Injection followed within 2 to 4 minutes by GEH200521 (18F) Injection followed by a 10mL saline flush 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. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Del A: Forekomsten af AE'er ved kausalitet til IMP'erne.
Tidsramme: Del A: 7 dage
|
Del A: 7 dage
|
|
Del A: Alvorligheden af AE'er i henhold til National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) efter kausalitet til IMP'erne.
Tidsramme: Del A: 7 dage
|
Del A: 7 dage
|
|
For at evaluere tidsforløbsændringerne i GEH200521 (18F) Injektionsoptagelse efter immun-checkpoint inhibitor (ICI) behandlingscyklusser sammenlignet med baseline.
Tidsramme: Del B: 50 dage
|
Del B: 50 dage
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
For at evaluere strålingsdosimetrien af en fast dosis GEH200521 (18F) Injection, når den administreres med de forskellige GEH200520 Injection massedoser efter kumuleret aktivitet i kilderegioner og af hele kroppen.
Tidsramme: 7 dage
|
7 dage
|
|
|
For at evaluere det optimale billeddannelsestidsvindue for GEH200521 (18F) Injection positron emission tomography (PET) billeddannelse, når det administreres med forskellige GEH200520 injektionsmassedoser til del A-personer.
Tidsramme: 7 dage
|
7 dage
|
|
|
For at bestemme den passende massedosis af GEH200520 Injection til administration med GEH200521 (18F) Injection for at opnå en acceptabel PET-billedkvalitet for Del A-emner.
Tidsramme: 7 dage
|
7 dage
|
|
|
For at vurdere immunogenicitet, via forekomsten af behandlingsinducerede anti-lægemiddel-antistof-responser, efter en enkelt injektion af de forskellige GEH200520-injektionsmassedoser administreret med en fast dosis GEH200521 (18F)-injektion til del A-individer.
Tidsramme: 7 dage
|
7 dage
|
|
|
Indsamling af forekomst, sværhedsgrad, ændringer mellem besøg for AE'er/SAE'er/AESI'er
Tidsramme: 50 dage
|
50 dage
|
|
|
For at vurdere biofordelingen og tumoroptagelsen af GEH200521 (18F) Injektion med den optimale GEH200520 Injektionsdosis bestemt i del A baseret på kvantitative målinger af GEH200521 (18F) i områder af interesse for del B-personer.
Tidsramme: 50 dage
|
50 dage
|
|
|
For at vurdere forholdet mellem tumor GEH200521 (18F) Injektionsoptagelse (SUV-værdi) og immuncelle CD8+-ekspressionsscore fra en biopsiprøve/resekeret læsion, når den er tilgængelig baseret på IHC-resultater for del B-personer.
Tidsramme: 50 dage
|
50 dage
|
|
|
For at sammenligne ændringer i tumor GEH200521 (18F) Injektionsoptagelse med ændringer i computertomografi (CT) billedvurdering i henhold til Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for del B-emner, når de er tilgængelige.
Tidsramme: 50 dage
|
50 dage
|
|
|
For at sammenligne ændringer i tumor GEH200521 (18F) Injektionsoptagelse med ændringer i computertomografi (CT) billedvurdering ifølge [18F]-fluordeoxyglucose (FDG)-scanninger, når det er tilgængeligt for del B-personer.
Tidsramme: 50 dage
|
50 dage
|
|
|
For at sammenligne immunogenicitet, via forekomsten af behandlingsinducerede anti-lægemiddel-antistof-responser, efter flere administrationer af GEH200520-injektion med GEH200521 (18F)-injektion for del B-individer.
Tidsramme: 50 dage
|
50 dage
|
|
|
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.
Tidsramme: 7 days
|
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.
Tidsramme: 7 days
|
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.
Tidsramme: 7 days
|
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.
Tidsramme: 7 days
|
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.
Tidsramme: 7 days
|
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.
Tidsramme: 7 days
|
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
Tidsramme: Baseline, 24 hours, 7 days post IMP administration
|
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.
Tidsramme: 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. |
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.
Tidsramme: 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. |
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
Tidsramme: Baseline, 2 hours, 24 hours, 7 days post IMP administration
|
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
Tidsramme: Baseline, 2 hours, 24 hours, 7 days post IMP administration
|
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
Tidsramme: Baseline, 2 hours, 24 hours, 7 days post IMP administration
|
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
Tidsramme: Baseline, 2 hours, 24 hours, 7 days post IMP administration
|
Descriptive statistics will be used to describe the observed values and change from baseline. |
Baseline, 2 hours, 24 hours, 7 days post IMP administration
|
|
Changes in physical examination status following administration of GEH200520 and GEH200521 (18F) for Part B subjects
Tidsramme: Baseline, Day 15, Day 36, Day 50
|
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.
Tidsramme: 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. |
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.
Tidsramme: 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. |
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
Tidsramme: Baseline, Day 15, Day 36, Day 50
|
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
Tidsramme: Baseline, Day 15, Day 36, Day 50
|
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
Tidsramme: Baseline, Day 15, Day 36, Day 50
|
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
Tidsramme: Baseline, Day 15, Day 36, Day 50
|
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.
Tidsramme: 50 days
|
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.
Tidsramme: 50 days
|
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.
Tidsramme: 50 days
|
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.
Tidsramme: 50 days
|
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.
Tidsramme: 50 days
|
The PK parameter to be assessed: t1/2 |
50 days
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Studieleder: Ravi Karra, MD, GE Healthcare
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- GE-269-001
- 2024-515218-42-00 (Ctis)
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