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GEN1046 sikkerhedsforsøg i patienter med ondartede solide tumorer

17. august 2026 opdateret af: Genmab

Først i mennesket, åbent, dosis-eskaleringsforsøg med ekspansionskohorter for at evaluere sikkerheden af ​​GEN1046 hos forsøgspersoner med ondartede solide tumorer

Formålet med forsøget er at evaluere sikkerheden af ​​GEN1046 som monoterapi og i kombinationsterapier hos patienter med ondartede solide tumorer

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Forsøget er et åbent, multicenter sikkerhedsforsøg af GEN1046. Forsøget består af to dele, en dosiseskaleringsdel (fase 1, først-i-menneske (FIH) og en ekspansionsdel (fase 2a)). Udvidelsesdelen af ​​forsøget vil blive påbegyndt, når den anbefalede fase 2-dosis (RP2D) er blevet bestemt.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

429

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

  • Forenede Stater
    • Arizona
      • Phoenix, Arizona, Forenede Stater, 85054
        • Mayo Clinic
    • Connecticut
      • New Haven, Connecticut, Forenede Stater, 06520-8028
        • Yale University Cancer Center
    • Florida
      • Jacksonville, Florida, Forenede Stater, 32224
        • Mayo Clinic
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Emory University
    • Iowa
      • Iowa City, Iowa, Forenede Stater, 52242
        • University of Iowa Hospitals
    • Kentucky
      • Louisville, Kentucky, Forenede Stater, 40202
        • Norton Healthcare Inc
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater, 48109
        • University of Michigan
      • Grand Rapids, Michigan, Forenede Stater, 49546
        • START MidWest
    • Minnesota
      • Rochester, Minnesota, Forenede Stater, 55905
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, Forenede Stater, 10016
        • NYU Langone
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater, 27514
        • UNC Chapel Hill
      • Charlotte, North Carolina, Forenede Stater, 28204
        • Levine Cancer Institute, Atrium Health
    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44106
        • University Hospitals Cleveland Medical Center
  • Georgien
      • Batumi, Georgien
        • High Technology Hospital Medcenter
      • Tbilisi, Georgien
        • LLC "TIM - Tbilisi Institute of Medicine"
      • Tbilisi, Georgien
        • LTD Consilium Medulla
      • Tbilisi, Georgien
        • Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd
  • Israel
      • Haifa, Israel
        • Rambam Health Care Campus RHCC - Rambam Medical Center
      • Jerusalem, Israel, 12000
        • Hadassah Medical Organization HMO - Sharett Institute of Oncology
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
      • Tel Litwinsky, Israel, 52621
        • Sheba Medical Center, Ramat Gan
  • Italien
      • Bologna, Italien
        • Policlinico San'Orsola
      • Milan, Italien
        • IRCCS - Istituto Europeo di Oncologia IEO
      • Naples, Italien
        • Istituto Nazionale Tumori - Fondazione Pascale Italy
      • Parma, Italien
        • Azienda Ospedaliero Universitaria di Parma
      • Ravenna, Italien
        • AUSL Romagno-Ravenna
      • Roma, Italien
        • Policlinico Uni. Campus Bio-Medico
      • Rome, Italien
        • Regina Elena National Cancer Institute
      • Varese, Italien
        • ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "
  • Polen
      • Gdansk, Polen
        • Uniwersyteckie Centrum Kliniczne
      • Poznan, Polen
        • Medpolonia Sp. z o.o.
      • Prabuty, Polen
        • Specialist Hospital in Prabuty
      • Szczecin, Polen
        • Dom Lekarski SA
      • Warsaw, Polen
        • Maria Sklodowska Curie National Research Instutute of Oncology
  • Spanien
      • Barcelona, Spanien, 08035
        • Hospital Universitario Vall Dhebron
      • Barcelona, Spanien, 8023
        • IOB-Hospital Quironsalud Barcelona
      • Madrid, Spanien, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spanien, 28040
        • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
      • Madrid, Spanien
        • MD Anderson Cancer Center Madrid
      • Madrid, Spanien
        • Hospital Universitario La Princesa
      • Madrid, Spanien, 28050
        • START Madrid-CIOCC
      • Madrid, Spanien, 28223
        • NEXT Oncology Madrid
      • Málaga, Spanien
        • Hospital Universitario Virgen de la Victoria
      • Pamplona, Spanien, 31008
        • Clinica Universidad de Navarra
      • Valencia, Spanien, 46010
        • Hospital Clínico de Valencia
  • Tjekkiet
      • Brno, Tjekkiet
        • Fakultni nemocnice Brno
      • Brno, Tjekkiet
        • University Hospital Brno
      • Nový Jičín, Tjekkiet
        • Nemocnice AGEL Ostrava-Vítkovice a.s.
      • Olomouc, Tjekkiet
        • Fakultni Nemocnice Olomouc
  • Tyrkiet (Türkiye)
      • Ankara, Tyrkiet (Türkiye)
        • Gulhane Training and Research Hospital
      • Cordaleo, Tyrkiet (Türkiye)
        • Medical Point Izmir Hospital
      • Edirne, Tyrkiet (Türkiye)
        • Trakya University Hospital
  • Ukraine
      • Kyiv, Ukraine
        • ARENSIA Exploratory Medicine LLC
  • Ungarn
      • Debrecen, Ungarn
        • Onkologiai Klinika
      • Kecskemét, Ungarn
        • BKMK Hospital
      • Törökbálint, Ungarn
        • Pulmonology Hospital Törökbálinti

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

14 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Nøgleinklusionskriterier:

Til dosiseskalering:

• Har en histologisk eller cytologisk bekræftet ikke-CNS solid tumor, der er metastatisk eller ikke-opererbar, og for hvem der ikke er tilgængelig standardbehandling

Til udvidelse:

• Har histologisk eller cytologisk bekræftet diagnose af recidiverende eller refraktær, fremskreden og/eller metastatisk NSCLC, EC, UC, TNBC, SCCHN eller livmoderhalskræft, som ikke længere er kandidater til standardterapi For to separate ekspansionskohorter: metastatisk NSCLC uden forudgående systemisk behandling regimer for metastatisk sygdom.

Til både dosiseskalering og -udvidelse

  • Har målbar sygdom i henhold til RECIST 1.1
  • Har Eastern Cooperative Oncology Group (ECOG) 0-1
  • Har en acceptabel hæmatologisk status
  • Har en acceptabel leverfunktion
  • Har en acceptabel koagulationsstatus
  • Har acceptabel nyrefunktion

Nøgleekskluderingskriterier:

  • Har ukontrolleret interkurrent sygdom, herunder men ikke begrænset til:

    • Igangværende eller aktiv infektion, der kræver intravenøs behandling med antiinfektiv terapi
    • Symptomatisk kongestiv hjertesvigt (grad III eller IV klassificeret af New York Heart Association), ustabil angina pectoris eller hjertearytmi
    • Ukontrolleret hypertension defineret som systolisk blodtryk ≥ 160 mmHg og/eller diastolisk blodtryk ≥ 100 mmHg, på trods af optimal medicinsk behandling
    • Igangværende eller nylige tegn på autoimmun sygdom
    • Anamnese med irAE'er, der førte til tidligere seponering af checkpoint-behandling
    • Tidligere myositis, Guillain-Barré syndrom eller myasthenia gravis af enhver grad
    • Anamnese med kronisk leversygdom eller tegn på levercirrhose
    • Anamnese med ikke-infektiøs pneumonitis, der har krævet steroider eller i øjeblikket har pneumonitis
    • Anamnese med organallotransplantat (undtagen hornhindetransplantation) eller autolog eller allogen knoglemarvstransplantation eller stamcelleredning inden for 3 måneder før den første dosis af GEN1046
    • Alvorligt, ikke-helende sår, hudsår (af enhver grad) eller knoglebrud
  • Enhver historie med intracerebral arteriovenøs misdannelse, cerebral aneurisme, nye (yngre end 6 måneder) eller progressive hjernemetastaser eller slagtilfælde

  • Tidligere terapi:

    • Strålebehandling: Strålebehandling inden for 14 dage før første GEN1046 administration. Palliativ strålebehandling vil være tilladt.
    • Behandling med et anti-cancermiddel (inden for 28 dage eller efter mindst 5 halveringstider af lægemidlet, alt efter hvad der er kortest), før GEN1046 administration. Accepterede undtagelser er bisfosfonater (f.eks. pamidronat, zoledronsyre osv.) og denosumab
  • Toksiciteter fra tidligere kræftbehandlinger, som ikke er løst tilstrækkeligt

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: N/A
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Dosiseskalering
Acasunlimab vil blive administreret som monoterapi.
Biologisk: Acasunlimab
Acasunlimab vil blive administreret intravenøst ​​én gang hver 21. dag (i udvalgte ekspansionskohorter vil acasunlimab blive administreret intravenøst ​​én gang hver 21. dag i de første 2 cyklusser og hver 42. dag i de efterfølgende cyklusser).
Andre navne:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Eksperimentel: Udvidelse
Acasunlimab vil blive administreret som monoterapi eller i kombination med enten docetaxel, pembrolizumab eller pembrolizumab + standard kemoterapi i separate ekspansionskohorter.
Biologisk: Acasunlimab
Acasunlimab vil blive administreret intravenøst ​​én gang hver 21. dag (i udvalgte ekspansionskohorter vil acasunlimab blive administreret intravenøst ​​én gang hver 21. dag i de første 2 cyklusser og hver 42. dag i de efterfølgende cyklusser).
Andre navne:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biologisk: Acasunlimab i kombination med docetaxel (i en enkelt ekspansionskohorte)
Acasunlimab og docetaxel vil blive administreret intravenøst ​​én gang hver 21. dag.
Andre navne:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biologisk: Acasunlimab i kombination med pembrolizumab (i en separat ekspansionskohorte)
Acasunlimab og pembrolizumab vil blive administreret intravenøst ​​hver 21. dag eller hver 42. dag.
Andre navne:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biologisk: Acasunlimab i kombination med pembrolizumab og standard kemoterapi (i separate ekspansionskohorter)
Acasunlimab og pembrolizumab og standard kemoterapi vil blive administreret intravenøst ​​én gang hver 21. dag i 4 cyklusser, efterfulgt af behandling med acasunlimab og pembrolizumab én gang hver 21. dag.
Andre navne:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)
Tidsramme: During first cycle (21 days)
In this trial, a DLT was defined as any grade 5 toxicity, grade 4 neutropenia lasting more than 7 days, grade 3 and 4 febrile neutropenia, grade 4 thrombocytopenia for minimal duration of 7 days, grade 3&4 hemorrhage associated with thrombocytopenia of ≥ grade 3 requiring platelet transfusion, grade 4 anemia, liver toxicity (transaminases and bilirubin elevations), grade 3 nausea that didn't respond to optimal antiemetic treatment within 7 days, grade ≥3 vomiting that didn't respond to optimal antiemetic treatment within 3 days, grade ≥3 diarrhea that didn't respond to optimal antidiarrheal treatment within 3 days, grade 3 immune-related adverse event (irAEs) that didn't improve to ≤ grade 1 within 7 days by appropriate care or with corticosteroids (with exceptions per protocol), any grade 4 irAE, any other ≥ grade 3 non-hematological adverse events (AE), which occurred during the first GEN1046 treatment cycle (with exceptions per protocol).
During first cycle (21 days)
Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Treatment-emergent Adverse Events (AEs)
Tidsramme: Up to approximately 5 years, 10 months
An AE was defined as any untoward medical occurrence in a 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. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 5 years, 10 months
Expansion Cohort 1: Objective Response Rate (ORR)
Tidsramme: Up to approximately 5 years, 10 months
ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumors (RECIST v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 millimeters (mm). PR was defined as ≥30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs.
Up to approximately 5 years, 10 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Combination Therapy Expansion Cohorts: Number of Participants With Treatment-emergent AEs
Tidsramme: Up to approximately 5 years, 10 months
An AE was defined as any untoward medical occurrence in a 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. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 5 years, 10 months
Dose Escalation: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046
Tidsramme: Cycle 1 and Cycle 2 (cycles were 21 days)
Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2.
Cycle 1 and Cycle 2 (cycles were 21 days)
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of GEN1046
Tidsramme: Cycle 1 and Cycle 2 (cycles were 21 days)
Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2.
Cycle 1 and Cycle 2 (cycles were 21 days)
Number of Participants With Anti-drug Antibodies (ADAs) to GEN1046
Tidsramme: Up to approximately 5 years, 10 months
Venous blood samples were collected for measurement of serum concentrations of ADAs. A participant was considered as positive overall status if: (i) negative at baseline and at least one positive post-baseline result; or (ii) positive at baseline and at least one positive post-baseline result with a titer higher than baseline.
Up to approximately 5 years, 10 months
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: ORR
Tidsramme: Up to approximately 5 years, 10 months
ORR was defined as the percentage of participants with BOR of CR or PR based on RECIST. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs.
Up to approximately 5 years, 10 months
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: Disease Control Rate (DCR)
Tidsramme: Up to approximately 5 years, 10 months
DCR was defined as the percentage of participants with confirmed BOR of CR, PR, or stable disease (SD) according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Follow-up measurements must have met the SD criteria at least once and for a minimum time period of 6 weeks (±7 days) after first treatment.
Up to approximately 5 years, 10 months
Duration of Response (DoR)
Tidsramme: Up to approximately 5 years, 10 months
DOR was defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurred earlier based on RECIST v1.1. DOR only applied to participants whose confirmed best overall response was CR or PR (i.e., responders).
Up to approximately 5 years, 10 months
Expansion Cohort 1: Progression Free Survival (PFS)
Tidsramme: Up to approximately 5 years, 10 months
PFS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to the first documented progression or death due to any cause, whichever occurred first based on RECIST version 1.1.
Up to approximately 5 years, 10 months
Expansion Cohort 1: Overall Survival (OS)
Tidsramme: Up to approximately 5 years, 10 months
OS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to death due to any cause.
Up to approximately 5 years, 10 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Genmab

Samarbejdspartnere

BioNTech SE

Efterforskere

  • Studieleder: Study Official, Genmab

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.

Generelle publikationer

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)

14. maj 2019

Primær færdiggørelse (Faktiske)

1. april 2025

Studieafslutning (Faktiske)

3. august 2026

Datoer for studieregistrering

Først indsendt

11. april 2019

Først indsendt, der opfyldte QC-kriterier

12. april 2019

Først opslået (Faktiske)

17. april 2019

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

9. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

17. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • GCT1046-01
  • 2023 (U.S. NIH-bevilling/kontrakt: GRAMMY Museum Foundation)
  • 2018 (U.S. NIH-bevilling/kontrakt)
  • 2018-003402-63 (EudraCT nummer)
  • MOH_2019-05-08_006011 (Registry Identifier: Clinical Research Site - mytrial)
  • 2023-509059-15 (Anden identifikator: EU Trial (CTIS) Number)

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.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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