Uno studio per valutare la sicurezza e la tollerabilità di GEH200520/GEH200521 (18F) quando utilizzato per scansioni PET in pazienti con tumori maligni solidi
Uno studio di fase 1a/1b, multicentrico, in aperto, di aumento della dose e di espansione della dose in pazienti con tumori maligni solidi per valutare la sicurezza e la tollerabilità dell'iniezione GEH200520/GEH200521 (18F), l'imaging PET, la farmacocinetica e le modifiche Imaging dopo il trattamento
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.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Tipo di studio
Tipo di studio
Iscrizione (Effettivo)
Iscrizione
Fase
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
-
Amsterdam, Olanda
- Amsterdam UMC
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Groningen, Olanda
- UMC Groningen
-
-
Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Diagnostico
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
|
Sperimentale: 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. |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Parte A: L'incidenza degli eventi avversi sulla causalità degli IMP.
Lasso di tempo: Parte A: 7 giorni
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Parte A: 7 giorni
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Parte A: La gravità degli eventi avversi secondo i Common Terminology Criteria for Adverse Events (NCI CTCAE versione 5.0) del National Cancer Institute in base alla causalità degli IMP.
Lasso di tempo: Parte A: 7 giorni
|
Parte A: 7 giorni
|
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Per valutare i cambiamenti nel corso del tempo nell'assorbimento dell'iniezione di GEH200521 (18F) dopo cicli di trattamento con inibitori del checkpoint immunitario (ICI) rispetto al basale.
Lasso di tempo: Parte B: 50 giorni
|
Parte B: 50 giorni
|
Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Valutare la dosimetria delle radiazioni di una dose fissa di GEH200521 (18F) Injection quando somministrata con le diverse dosi di massa di GEH200520 Injection per attività cumulativa nelle regioni di origine e per tutto il corpo.
Lasso di tempo: 7 giorni
|
7 giorni
|
|
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Valutare la finestra temporale ottimale per l'imaging per l'imaging con tomografia a emissione di positroni (PET) GEH200521 (18F) quando somministrato con diverse dosi di massa per iniezione GEH200520 per i soggetti della Parte A.
Lasso di tempo: 7 giorni
|
7 giorni
|
|
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Determinare la dose di massa appropriata di GEH200520 Injection per la somministrazione con GEH200521 (18F) Injection per ottenere una qualità dell'immagine PET accettabile per i soggetti della Parte A.
Lasso di tempo: 7 giorni
|
7 giorni
|
|
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Per valutare l'immunogenicità, attraverso l'incidenza delle risposte anticorpali anti-farmaco indotte dal trattamento, dopo una singola iniezione delle diverse dosi di massa di iniezione GEH200520 somministrate con una dose fissa di iniezione GEH200521 (18F) per i soggetti della Parte A.
Lasso di tempo: 7 giorni
|
7 giorni
|
|
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Raccolta dell'incidenza, della gravità, dei cambiamenti tra le visite per AE/SAE/AESI
Lasso di tempo: 50 giorni
|
50 giorni
|
|
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Per valutare la biodistribuzione e l'assorbimento tumorale di GEH200521 (18F) Iniezione con la dose ottimale di iniezione GEH200520 determinata nella Parte A sulla base di misurazioni quantitative di GEH200521 (18F) nelle regioni di interesse per i soggetti della Parte B.
Lasso di tempo: 50 giorni
|
50 giorni
|
|
|
Valutare la relazione tra l'assorbimento dell'iniezione del tumore GEH200521 (18F) (valore SUV) e il punteggio di espressione CD8+ delle cellule immunitarie da un campione bioptico/lesione resecata, se disponibile, sulla base dei risultati IHC per i soggetti della Parte B.
Lasso di tempo: 50 giorni
|
50 giorni
|
|
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Per confrontare i cambiamenti nella captazione dell'iniezione GEH200521 (18F) del tumore con i cambiamenti nella valutazione dell'immagine della tomografia computerizzata (TC), secondo i criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1 per i soggetti della Parte B quando disponibili.
Lasso di tempo: 50 giorni
|
50 giorni
|
|
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Per confrontare i cambiamenti nella captazione dell'iniezione GEH200521 (18F) del tumore con i cambiamenti nella valutazione dell'immagine della tomografia computerizzata (TC), secondo le scansioni [18F]-fluorodeossiglucosio (FDG), quando disponibili per i soggetti della Parte B.
Lasso di tempo: 50 giorni
|
50 giorni
|
|
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Per confrontare l'immunogenicità, attraverso l'incidenza delle risposte anticorpali anti-farmaco indotte dal trattamento, dopo somministrazioni multiple di GEH200520 Injection con GEH200521 (18F) Injection per i soggetti della Parte B.
Lasso di tempo: 50 giorni
|
50 giorni
|
|
|
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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 50 days
|
The PK parameter to be assessed: t1/2 |
50 days
|
Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Direttore dello studio: Ravi Karra, MD, GE Healthcare
Studiare le date dei record
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Inizio studio (Effettivo)
Inizio studio
Completamento primario (Effettivo)
Completamento primario
Completamento dello studio (Effettivo)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- GE-269-001
- 2024-515218-42-00 (Ctis)
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