Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Anti-HER2 bispecifikt antistof ZW25 aktivitet i kombination med kemoterapi med/uden Tislelizumab

12. august 2026 opdateret af: BeiGene

Fase 1b/2-undersøgelse, der undersøger sikkerhed, tolerabilitet, farmakokinetik og foreløbig antitumoraktivitet af anti-HER2 bispecifikt antistof ZW25 i kombination med kemoterapi med/uden Tislelizumab hos patienter med avanceret HER2-positiv brystkræft eller gastrisk/gastroøsofageal Junction Adenocarcinoma

Formålet med studiet er at vurdere sikkerheden, tolerabiliteten og den foreløbige antitumoraktivitet af ZW25 i kombination med docetaxel hos deltagere med human epidermal vækstfaktor receptor 2 (HER2)-positiv brystkræft, og ZW25 i kombination med tislelizumab og kemoterapi hos deltagere med HER2-positiv gastrisk/gastroøsofageal Junction (GEJ) adenokarcinom

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

71

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

  • Kina
    • Beijing Municipality
      • Beijing, Beijing Municipality, Kina, 100142
        • Beijing Cancer Hospital
      • Beijing, Beijing Municipality, Kina, 100071
        • The Affiliated Hospital of Military Medical Sciences
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, Kina, 400030
        • Chongqing Cancer Hospital
    • Guangdong
      • Guangzhou, Guangdong, Kina, 510120
        • Guangdong Provincial Peoples Hospital Huifu Branch
    • Jiangxi
      • Nanchang, Jiangxi, Kina, 330009
        • The Third Hospital of Nanchang
    • Jilin
      • Changchun, Jilin, Kina, 130021
        • Jilin cancer hospital
    • Liaoning
      • Shenyang, Liaoning, Kina, 110042
        • Liaoning Cancer Hospital and Institute
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310022
        • Zhejiang Cancer Hospital
  • Sydkorea
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Sydkorea, 10408
        • National Cancer Center
      • Seongnam-si, Gyeonggi-do, Sydkorea, 13620
        • Seoul National University Bundang Hospital
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 03080
        • Seoul National University Hospital
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 05505
        • Asan Medical Center
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 06273
        • Gangnam Severance Hospital, Yonsei University Health System
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 06351
        • Samsung Medical Center
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 03722
        • Severance Hospital Yonsei University Health System
      • Seoul, Seoul Teugbyeolsi, Sydkorea, 08308
        • Korea University Guro Hospital
  • Taiwan
      • Kaohsiung City, Taiwan, 83301
        • Kaohsiung Chang Gung Memorial Hospital
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 100225
        • National Taiwan University Hospital East Campus

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:

  1. Sygdomsdiagnose og forudgående behandling:

    1. Kohorte 1 (kohorten til førstelinjebehandling af brystkræft):

      • Kvindelige deltagere med histologisk eller cytologisk bekræftet inoperabel, lokalt fremskreden, recidiverende eller metastatisk adenokarcinom i brystet og kandidat til kemoterapi. Lokalt tilbagevendende sygdom må ikke være modtagelig for resektion med helbredende hensigt.
      • Human epidermal vækstfaktor receptor 2 (HER2) IHC 3+ eller in situ hybridisering positiv på arkivtumorvæv eller frisk biopsiprøve.
      • Har ikke modtaget tidligere systemisk anticancerbehandling for lokalt fremskreden inoperabel eller metastatisk sygdom.

    2. Kohorte 2 (første-linje gastrisk/gastroøsofageal junction adenocarcinoma behandlingskohorte):

      • Histologisk eller cytologisk bekræftet uoperabelt, lokalt fremskredent, tilbagevendende eller metastatisk adenokarcinom i maven eller den gastroøsofageale forbindelse
      • HER2 IHC 3+ eller HER2 IHC 2+ sammen med in situ hybridiseringspositiv på arkivtumorvævet eller frisk biopsiprøve.
      • Har ikke modtaget tidligere systemisk anticancerbehandling for lokalt fremskreden inoperabel eller metastatisk sygdom, inklusive nogen godkendt eller undersøgt estimeret glomerulær filtrationshastighed (EGFR) eller anti-HER2-midler eller -vacciner, cytotoksisk kemoterapi eller checkpoint-hæmmere
  2. Mindst 1 målbar læsion som defineret i RECIST version 1.1
  3. Eastern Cooperative Oncology Group (ECOG) præstationsstatus ≤ 1
  4. Tilstrækkelig organfunktion som angivet af følgende laboratorieværdier under screening:
  5. Venstre ventrikulær ejektionsfraktion (LVEF) ≥ 50 % ved baseline som bestemt ved enten ekkokardiogram eller multigated acquisition scan (MUGA) (ekkokardiogram er den foretrukne metode) inden for 28 dage før den første dosis af undersøgelseslægemidlet

Nøgleekskluderingskriterier:

  1. Forudgående terapi med en anti-PD-1, anti-PD-L1, anti-PD-L2 eller ethvert andet antistof eller lægemiddel, der specifikt er målrettet mod T-celle co-stimulering eller checkpoint pathways

  2. Anamnese med godkendte eller undersøgende tyrosinkinase/HER-hæmmere i enhver behandlingssituation

    en. undtagen trastuzumab med eller uden pertuzumab brugt i neoadjuverende eller adjuverende omgivelser til kohorte 1

  3. Aktiv leptomeningeal sygdom, ubehandlet eller ukontrolleret hjernemetastase
  4. Enhver aktiv malignitet ≤ 2 år før den første dosis af undersøgelseslægemidlet, bortset fra den specifikke cancer, der undersøges i dette forsøg og enhver lokaliseret cancer, der er blevet behandlet kurativt (f.eks. resekeret basal- eller pladecellehudkræft, overfladisk blærekræft, karcinom i situ af livmoderhalsen eller brystet)
  5. Enhver tilstand, der krævede systemisk behandling med enten kortikosteroider (> 10 mg dagligt prednison eller tilsvarende) eller anden immunsuppressiv medicin ≤ 14 dage før den første dosis af undersøgelseslægemidlet

Bemærk: Deltagere, der i øjeblikket eller tidligere har været på et af følgende steroidregimer, er ikke udelukket:

  1. Adrenal erstatningssteroid (dosis ≤ 10 mg dagligt af prednison eller tilsvarende)
  2. Topisk, okulær, intraartikulær, intranasal eller inhaleret kortikosteroid med minimal systemisk absorption
  3. Kort kur (≤ 7 dage) med kortikosteroid ordineret profylaktisk (f.eks. mod kontrastfarveallergi) eller til behandling af en ikke-autoimmun tilstand (f.eks. forsinket overfølsomhedsreaktion forårsaget af kontaktallergen)

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: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Cohort 1A: Breast Cancer: Zanidatamab 30 mg/kg + Docetaxel
Participants with HER2+ breast cancer received zanidatamab 30 mg/kg intravenously (IV) and docetaxel 75 mg/m^2 IV once every 3 weeks (Q3W) for an initial period of up to six cycles. After cycle 6, continuation of docetaxel treatment was at the discretion of the investigator. Zanidatamab was administered until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met.
Medicin: Docetaxel
Indgives intravenøst
Biologisk: Zanidatamab
Indgives intravenøst
Andre navne:
  • ZW25
Eksperimentel: Cohort 1B: Breast Cancer: Zanidatamab 1800 mg + Docetaxel
Participants with HER2+ breast cancer received zanidatamab 1800 mg/kg IV and docetaxel 75 mg/m^2 IV Q3W for an initial period of up to six cycles. After cycle 6, continuation of docetaxel treatment was at the discretion of the investigator. Zanidatamab was administered until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met.
Medicin: Docetaxel
Indgives intravenøst
Biologisk: Zanidatamab
Indgives intravenøst
Andre navne:
  • ZW25
Eksperimentel: Cohort 2A: Gastric/GEJC: Zanidatamab 30 mg/kg + Tislelizumab + CAPOX
Participants with HER2+ gastric / gastroesophageal junction cancer (GEJC) received zanidatamab 30 mg/kg IV and tislelizumab 200 mg IV once every 3 weeks until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met. Participants also received CAPOX chemotherapy (1000 mg/m^2 oral capecitabine twice daily for 14 days in each cycle and 130 mg/m^2 oxaliplatin IV once every 3 weeks) for up to 6 six cycles. After cycle 6, oxaliplatin was discontinued and continuation of capecitabine as maintenance treatment was at the investigator's discretion.
Medicin: Capecitabin
Indgives oralt
Medicin: Oxaliplatin
Indgives intravenøst
Biologisk: Zanidatamab
Indgives intravenøst
Andre navne:
  • ZW25
Biologisk: Tislelizumab
Indgives intravenøst
Andre navne:
  • BGB-A317
Eksperimentel: Cohort 2B: Gastric/GEJC : Zanidatamab 1800/2400 mg + Tislelizumab + CAPOX
Participants with HER2+ gastric / GEJC received zanidatamab 1800 mg (participants with body weight < 70 kg) or 2400 mg (participants with body weight ≥ 70 kg) IV and tislelizumab 200 mg IV Q3W until disease progression, intolerable toxicity, or another criterion for treatment discontinuation was met. Participants also received CAPOX chemotherapy (1000 mg/m^2 oral capecitabine twice daily for 14 days in each cycle and 130 mg/m^2 oxaliplatin IV once every 3 weeks) for up to 6 six cycles. After cycle 6, oxaliplatin was discontinued and continuation of capecitabine as maintenance treatment was at the investigator's discretion.
Medicin: Capecitabin
Indgives oralt
Medicin: Oxaliplatin
Indgives intravenøst
Biologisk: Zanidatamab
Indgives intravenøst
Andre navne:
  • ZW25
Biologisk: Tislelizumab
Indgives intravenøst
Andre navne:
  • BGB-A317

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatments, whether considered related to study treatments or not.

A serious AE (SAE) was any untoward medical occurrence that, at any dose - resulted in death, - was life threatening, - required hospitalization or prolongation of existing hospitalization, - resulted in disability/incapacity, - was a congenital anomaly/birth defect.
From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months
Objective Response Rate (ORR)
Tidsramme: Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42months.

ORR is defined as the percentage of participants who had a best overall response of complete response or partial response per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42months.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Duration of Response (DOR)
Tidsramme: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
DOR is defined as the time from the first determination of an objective response until the first documentation of disease progression or death, whichever occurred first.
From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
Time to Response (TTR)
Tidsramme: From the start date of study treatment to the first documentation of response, whichever occurs first, up to approximately 42 months
Time to response is defined as the time from the start date of study treatment to the first determination of an objective response assessed by investigator per RECIST v 1.1.
From the start date of study treatment to the first documentation of response, whichever occurs first, up to approximately 42 months
Progression-free Survival (PFS)
Tidsramme: From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
PFS is defined as the time from the start date of study drug to the date of the first objectively documented tumor progression assessed by investigator per RECIST Version 1.1 or death, whichever occurred first.
From the start date of study treatment to the first documentation of progression or death, whichever occurs first, up to approximately 42 months
Disease Control Rate (DCR)
Tidsramme: Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42 months.

DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR, and stable disease by investigator per RECIST Version 1.1.

BOR is the best response recorded from the start of the study drug treatment until the end of treatment taking into account any requirement for confirmation.
Response was assessed every 6 weeks from cycle 1 day 1 for the first 36 weeks and then every 12 weeks thereafter; maximum time on study follow-up was 42 months.
Overall Survival (OS)
Tidsramme: From the start date of study treatment to the documented death date or the last known alive date, up to approximately 41 months
Time from the start date of study drug to the date of death due to any cause.
From the start date of study treatment to the documented death date or the last known alive date, up to approximately 41 months
Serum Concentration of Zanidatamab as a Function of Time
Tidsramme: Day 1 end of infusion of Cycle 1, 2, 5, 9, 17, 26 and 35. Each cycle is 21 days
Day 1 end of infusion of Cycle 1, 2, 5, 9, 17, 26 and 35. Each cycle is 21 days
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Timepoint (AUC(0-t)) of Zanidatamab
Tidsramme: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Observed Maximum Plasma Concentration of Zanidatamab During a Sample Interval (Cmax)
Tidsramme: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Observed Time to Maximum Plasma Concentration of Zanidatamab During a Sampling Interval (Tmax)
Tidsramme: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Terminal Elimination Half-life (t1/2) of Zanidatamab
Tidsramme: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose. Cycle 2: predose and 0, 168, and 336 hours postdose. Each cycle is 21 days.
Apparent Clearance After Oral Administration (CL/F) of Zanidatamab
Tidsramme: Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose
Cycle 1: predose and 0, 2, 4, 24, 96, 168, and 336 hours postdose
Number of Participants With Anti-zanidatamab Antibodies
Tidsramme: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months
From the first dose of study drug(s) to 30 days after the last dose; up to approximately 42 months
Number of Participants With AEs and SAEs in Participants Who Entered the Long-term Extension Period
Tidsramme: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 51 months
From the first dose of study drug(s) to 30 days after the last dose; up to approximately 51 months

Samarbejdspartnere og efterforskere

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

Sponsor

BeiGene

Efterforskere

  • Studieleder: Study Director, BeiGene

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)

23. marts 2020

Primær færdiggørelse (Faktiske)

7. december 2023

Studieafslutning (Faktiske)

31. oktober 2024

Datoer for studieregistrering

Først indsendt

4. februar 2020

Først indsendt, der opfyldte QC-kriterier

18. februar 2020

Først opslået (Faktiske)

19. februar 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

2. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • BGB-A317-ZW25-101
  • CTR20210237 (Anden identifikator: ChinaDrugTrials)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

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

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 .

Abonner