Et sikkerheds- og antitumoraktivitetsforsøg med immunradioterapikombinationer som en behandlingsmulighed for forsøgspersoner med metastatiske solide tumorer
10. august 2026 opdateret af: Genmab
En fase 1-dosisfinding og fase 2, randomiseret, åbent-label forsøg til evaluering af sikkerheden og den kliniske aktivitet af immunradioterapikombinationer som en behandlingsmulighed hos forsøgspersoner med metastatiske solide tumorer
At evaluere sikkerheden og den kliniske aktivitet af GEN1042 i kombination med strålebehandling med eller uden pembrolizumab som en behandlingsmulighed for patienter med metastaserende solide tumorer
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsen vil blive udført i to dele: del 1 (dosis-finding) og del 2 (randomisering).
Del 1 vil evaluere sikkerheden ved kombinationer af immunradioterapi og fastlægge de(n) dosis(er), der skal evalueres i del 2.
Del 2 vil evaluere antitumoraktiviteten af immunradioterapikombinationer ved de(n) fastsatte dosis(er) fra del 1.
Deltagere i begge dele behandles med en af følgende kombinationer:
- Strålebehandling + GEN1042
- Strålebehandling + GEN1042 + pembrolizumab
Mens deltagerne i del 1 tildeles sekventielt (GEN1042 uden pembrolizumab undersøges først), er deltagerne i del 2 randomiseret 1:1 i de to behandlingsarme
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
13
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Lyon, Frankrig, 69008
- Centre Leon Berard
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Villejuif, Frankrig, 94805
- Institut Gustave Roussy
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Beskrivelse
Nøgleinklusionskriterier:
- Deltagere med histologisk bekræftet ikke-CNS solid tumor, der er metastatisk, og for hvem der ikke er tilgængelig standardbehandling
- Mindst 18 år
- Underskrevet informeret samtykke forud for eventuelle screeningsprocedurer
- Målbar sygdom i henhold til RECIST v 1.1
- Forventet levetid på >3 måneder
- Kvalificere dig til palliativ strålebehandling som en tilgængelig mulighed for sygdomsbehandling
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Normal eller tilstrækkelig lever-, nyre-, hjerte- og knoglemarvsfunktion
Nøgleekskluderingskriterier:
- Tidligere malignitet bortset fra ikke-melanom hudkræft og in situ cancer
- Tilstand kontraindicerende strålebehandling
- Hurtigt fremadskridende sygdom
- Aktiv, kendt eller mistænkt autoimmun sygdom
- Anamnese med ikke-infektiøs pneumonitis, der krævede steroider eller i øjeblikket har pneumonitis
- Kontraindikationer til brugen af pembrolizumab
- Tilstand, der kræver systemisk behandling med enten kortikosteroider eller anden immunsuppressiv medicin inden for 14 dage efter første behandling
- Modtog en allogen væv/fast organtransplantation
- Aktiv infektion, der kræver systemisk terapi
Bemærk: Andre protokoldefinerede inklusions-/eksklusionskriterier kan være gældende.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Strålebehandling + GEN1042
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Strålebehandling
Intravenøs
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Eksperimentel: Strålebehandling + GEN1042 + Pembrolizumab
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Strålebehandling
Intravenøs
Intravenøs
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities (DLTs)
Tidsramme: 21 days
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A DLT was defined as any grade 5 toxicity, treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1, febrile neutropenia grade 3 or grade 4, grade 3 thrombocytopenia associated with clinically significant bleeding, grade 4 thrombocytopenia of any duration, grade 4 anemia, any grade ≥3 non-hematologic clinical (non-laboratory) toxicity with exceptions per protocol, any grade 3 or grade 4 non-hematologic laboratory value if clinically significant medical intervention was required to treat the participant or the abnormality led to hospitalization, or the abnormality persisted for >7 days, and the abnormality resulted in a drug-induced liver injury (DILI) as defined by Hy's Law.
Toxicities were graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
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21 days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Objective Response Rate (ORR)
Tidsramme: Up to approximately 2 years 5 months
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ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) v1.1 as assessed by investigator.
CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to <10 millimeters (mm) in all pathological target and non-target lesions.
PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Up to approximately 2 years 5 months
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Duration of Response (DOR)
Tidsramme: Up to approximately 2 years 5 months
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DOR was defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
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Up to approximately 2 years 5 months
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Disease Control Rate (DCR)
Tidsramme: Up to approximately 2 years 5 months
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DCR was defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1 as assessed by investigator.
CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to <10 millimeters (mm) in all pathological target and non-target lesions.
PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
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Up to approximately 2 years 5 months
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Progression Free Survival (PFS)
Tidsramme: Up to approximately 2 years 5 months
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PFS was defined as the time from the date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
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Up to approximately 2 years 5 months
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Overall Survival (OS)
Tidsramme: Up to approximately 2 years 5 months
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OS was defined as the time from date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to date of death due to any cause.
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Up to approximately 2 years 5 months
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Number of Participants With Abscopal Response in Non-irradiated Target Lesions As Assessed by the Investigator
Tidsramme: Up to approximately 2 years 5 months
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An abscopal response described radiotherapy (RT)-induced immune-mediated tumor regression at sites distant to the irradiated field.
For the purpose of this trial, an abscopal response was defined as a reduction of at least 30% in diameter of the best responding unirradiated target lesion.
Data are reported for the number of participants with abscopal response in non-irradiated target lesions as assessed by the investigator.
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Up to approximately 2 years 5 months
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Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Tidsramme: Up to approximately 2 years 5 months
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An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
A TEAE was any AE that occurred or worsened after the first dose of trial treatment.
A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section.
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Up to approximately 2 years 5 months
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Blood Concentration of GEN1042 Over Time
Tidsramme: At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length.
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Blood samples were collected for measurement of serum concentrations of GEN1042.
Data are reported for Cycle (C)1 Day (D)1 pre-dose and end of infusion (EOI), C1D8, C1D15, C2D1 pre-dose and end of infusion, C2D8, C2D15, C3D1 pre-dose and end of infusion,C4D1 pre-dose and end of infusion,C4D8, C5D1 pre-dose and end of infusion, C7D1 pre-dose and end of infusion,C11D1 end of infusion,C12D1 end of infusion+2 hours,C15D1 end of infusion,C19D1 end of infusion,C23D1 end of infusion, End of Treatment (~D487) and Safety Follow Up (~D517).
Cycles were 21 days in length.
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At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length.
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Number of Participants With Anti-drug Antibodies (ADAs)
Tidsramme: Up to approximately 2 years 5 months
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Venous blood samples were drawn for analysis of ADAs.
Data are reported for the number of participants with an on-treatment ADA status of positive.
For on-treatment results, a participant was considered ADA positive if either 1) ADA was negative at baseline and at least one on-treatment result was positive 2) positive at baseline and at least one positive on-treatment result with at least one titer higher than baseline.
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Up to approximately 2 years 5 months
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
8. marts 2023
Primær færdiggørelse (Faktiske)
11. august 2025
Studieafslutning (Faktiske)
11. august 2025
Datoer for studieregistrering
Først indsendt
4. august 2022
Først indsendt, der opfyldte QC-kriterier
4. august 2022
Først opslået (Faktiske)
8. august 2022
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
12. august 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
10. august 2026
Sidst verificeret
1. juni 2026
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- GCT1042-02
- 2022-000509-29 (EudraCT nummer)
- 2023-508529-29-00 (Ctis)
- RECF-005058 (Registry Identifier: National Institute of Cancer France)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
INGEN
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
produkt fremstillet i og eksporteret fra U.S.A.
Ja
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