En fase I-dosisoptrapnings- og dosisudvidelsesundersøgelse til undersøgelse af farmakokinetikken og sikkerheden af subkutan Durvalumab (IMFINZI-subQ)
En fase I, multicentrisk, doseeskalerings- og doseekspansionsundersøgelse til undersøgelse af farmakokinetik og sikkerhed af subkutan durvalumab hos voksne deltagere med solide tumores
The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
This is a Phase I, multicentre study that will consist of 2 parts -
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).
Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: AstraZeneca Clinical Study Information Center
- Telefonnummer: 1-877-240-9479
- E-mail: information.center@astrazeneca.com
Studiesteder
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Fitzroy, Australien, 3065
- Trukket tilbage
- Research Site
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St Albans, Australien, 3021
- Trukket tilbage
- Research Site
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Woolloongabba, Australien, 4102
- Trukket tilbage
- Research Site
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Batumi, Georgien, 6010
- Rekruttering
- Research Site
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Tbilisi, Georgien, 0114
- Rekruttering
- Research Site
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Tbilisi, Georgien, 0112
- Rekruttering
- Research Site
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Brzozów, Polen, 36-200
- Rekruttering
- Research Site
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Koszalin, Polen, 75-581
- Rekruttering
- Research Site
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Lublin, Polen, 20-090
- Rekruttering
- Research Site
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Olsztyn, Polen, 10-357
- Rekruttering
- Research Site
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Przemyśl, Polen, 37-700
- Rekruttering
- Research Site
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Seongnam-si, Sydkorea, 13620
- Rekruttering
- Research Site
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Seoul, Sydkorea, 06351
- Rekruttering
- Research Site
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Seoul, Sydkorea, 5505
- Rekruttering
- Research Site
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Seoul, Sydkorea, 03722
- Rekruttering
- Research Site
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Tainan, Taiwan, 73657
- Rekruttering
- Research Site
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Taipei, Taiwan, 112
- Trukket tilbage
- Research Site
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Taipei, Taiwan, 110
- Rekruttering
- Research Site
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Taoyuan, Taiwan, 333
- Trukket tilbage
- Research Site
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of ≥ 12 weeks at enrolment.
- Adequate organ and marrow function.
- Minimum body weight > 30 kg.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
- Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
- Have not progressed following definitive concurrent chemoradiation.
LS-SCLC Participants -
- Histologically or cytologically documented LS-SCLC (Stage I-III).
- Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
- Have not progressed following definitive concurrent chemoradiation.
Part 1 and 2:
Unresectable HCC Participants -
- Unresectable HCC based on histopathological confirmation.
- No prior systemic therapy for unresectable HCC.
- Must not be eligible for locoregional therapy for unresectable HCC.
- Child-Pugh Score class A.
- Measurable disease as defined by RECIST v1.1.
Exclusion Criteria:
- Active or prior documented autoimmune disease requiring systemic treatment.
- Uncontrolled infection (including human immunodeficiency virus [HIV], hepatitis B or C).
- Prior exposure to immune checkpoint inhibitors.
Part 1 only:
Locally Advanced Unresectable (Stage III) NSCLC Participants -
- Mixed SCLC and NSCLC histology.
- Active pneumonitis or interstitial lung disease requiring systemic therapy.
LS SCLC Participants -
- Mixed SCLC and NSCLC histology.
- Extensive-stage disease.
- History of Grade ≥ 2 pneumonitis.
Part 1 and 2:
Unresectable HCC Participants -
- Hepatic encephalopathy.
- Uncontrolled ascites.
- Active gastrointestinal (GI) bleeding.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Andre navne:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
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Eksperimentel: Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Andre navne:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
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Eksperimentel: Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals. |
Durvalumab + rHu will be administered subcutaneously. Durvalumab will be administered intravenously.
Andre navne:
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Area under the concentration-time curve
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUC of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Observed lowest concentration before the next dose is administered (Ctrough)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Ctrough of SC durvalumab |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the AUClast of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Maximum observed concentration (Cmax)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Time to reach maximum concentration following drug administration (tmax)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the tmax of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Terminal elimination half-life (t1/2λz)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the t1/2λz of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Total body clearance/apparent total body clearance (CL[/F])
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the CL(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Apparent volume of distribution based on the terminal phase volume (Vz[/F])
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the VZ(/F) of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Average drug concentration over a dosing interval (Cavg)
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the Cavg of SC durvalumab. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Serum concentration of durvalumab
Tidsramme: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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To characterise the serum concentration of SC durvalumab at specified timepoints. |
From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
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Number of participants with adverse events (AEs)
Tidsramme: Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
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Number of participants with dose-limiting toxicities (DLTs)
Tidsramme: Up to Survival Follow-up (approximately 17 months)
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To assess the safety and tolerability of SC durvalumab. |
Up to Survival Follow-up (approximately 17 months)
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
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
Nøgleord
Yderligere relevante MeSH-vilkår
- Neoplasmer efter sted
- Neoplasmer
- Luftvejssygdomme
- Neoplasmer efter histologisk type
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Lungesygdomme
- Leversygdomme
- Neoplasmer, kirtel og epitel
- Adenocarcinom
- Neoplasmer i leveren
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Lungeneoplasmer
- Karcinom
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Carcinom, hepatocellulært
- Karcinom, ikke-småcellet lunge
- Småcellet lungekarcinom
- Durvalumab
- tremelimumab
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- D907HC00001
- 2025-521639-34-00 (Anden identifikator: EU CT number)
- 2025 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD-delingstidsramme
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD-delingsadgangskriterier
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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