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En sikkerhet og effektstudie av ZW25 (Zanidatamab) Pluss kombinasjonskjemoterapi ved HER2-uttrykkende gastrointestinale kreftformer, inkludert gastroøsofagealt adenokarsinom, galleveiskreft og tykktarmskreft

13. oktober 2026 oppdatert av: Jazz Pharmaceuticals

Fase 2-studie av ZW25 Plus førstelinjekombinasjonskjemoterapi ved HER2-uttrykkende gastrointestinal (GI) kreft, inkludert gastroøsofagealt adenokarsinom (GEA), galleveiskreft (BTC) og kolorektal kreft (CRC)

This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) plus standard first-line combination chemotherapy regimens for selected gastrointestinal (GI) cancers. Eligible patients include those with unresectable, locally advanced, recurrent or metastatic HER2-expressing gastroesophageal adenocarcinoma (GEA), biliary tract cancer (BTC), or colorectal cancer (CRC).

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus standard first-line combination chemotherapy (XELOX, FP, or mFOLFOX6 for GEA; mFOLFOX6 with or without bevacizumab for CRC; and CisGem for BTC) and will confirm the recommended dosage (RD) of ZW25 when administered in combination with each of these multi-agent chemotherapy regimens. Then, Part 2 of the study will evaluate the anti-tumor activity of ZW25 plus combination chemotherapy in HER2-expressing GEA, BTC, and CRC.

Studietype

Intervensjonell

Registrering (Faktiske)

74

Fase

  • Fase 2

Utvidet tilgang

Ikke lenger tilgjengelig utenfor den kliniske utprøvingen. Se utvidet tilgangspost.

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M5G 2C1
        • Princess Margaret Cancer Center
  • Chile
      • Santiago, Chile, 8241479
        • Icegclinic Research & Care
      • Santiago, Chile, 8420383
        • Centro Internacional de Estudios Clínicos
      • Santiago, Chile, 7500653
        • Centro de Investigacion Clinica SAGA
      • Santiago, Chile, 8320000
        • CECIM Biocinetic
  • Forente stater
    • California
      • Los Angeles, California, Forente stater, 90033
        • USC/Norris Comprehensive Cancer Center
      • Newport Beach, California, Forente stater, 92663
        • Hoag Memorial Hospital Presbyterian
    • Florida
      • Tampa, Florida, Forente stater, 33612
        • H. Lee Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, Forente stater, 60637
        • University of Chicago
    • Michigan
      • Grand Rapids, Michigan, Forente stater, 49503
        • The Cancer and Hematology Centers
    • Nebraska
      • Omaha, Nebraska, Forente stater, 68114
        • Nebraska Methodist Hospital
    • New York
      • New York, New York, Forente stater, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, Forente stater, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Forente stater, 98101
        • Virginia Mason Medical Center
  • Sør -Korea
      • Busan, Sør -Korea, 49241
        • Pusan National University
      • Seoul, Sør -Korea, 03080
        • Seoul National University Hospital
      • Seoul, Sør -Korea, 05505
        • Asan Medical Center
      • Seoul, Sør -Korea, 03722
        • Severance Hospital
      • Seoul, Sør -Korea, 02841
        • Korea University Anam Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Sør -Korea, 13620
        • Seoul National University Bundang Hospital

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion:

  • Disease diagnosis:

    • Part 1:
    • GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+ or 2+ with or without gene amplification based upon local assessment or central assessment)
    • BTC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing BTC (including intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder cancer [GBC]) (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment)
    • CRC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing CRC (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment). Patients will be required to be extended RAS (KRAS and NRAS) and BRAF wild-type based upon central assessment.
    • Part 2:
    • GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+, or IHC 2+ and FISH+ by central assessment)
    • BTC: Same as Part 1
    • CRC: Same as Part 1

  • Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1:

    • Part 1: Measurable or non-measurable disease
    • Part 2: Measurable disease

  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

  • Adequate organ function

  • Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal

Exclusion:

  • Prior treatment with a HER2-targeted agent

  • Prior systemic anti-cancer therapy (including investigational products) except prior adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to first study treatment dosing. For subjects with BTC and CRC the following additional exceptions apply:

    • BTC: patients may have started therapy for advanced disease but may not have received more than one cycle of any standard gemcitabine-based chemotherapy regimen.
    • CRC: patients may have started therapy for advanced disease but may not have received more than one cycle of 5-FU-based chemotherapy (< 1 month of therapy).

  • Patients with certain contraindications to bevacizumab cannot be enrolled on the mFOLFOX6-2 with bevacizumab arm.

  • Palliative radiotherapy is allowed if completed at least 2 weeks prior to first study treatment dosing

  • Untreated known brain metastases (patients with treated brain metastases who are off steroids, off antiseizure medications, and stable for at least 1 month at the time of screening are eligible)

  • Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). Patients with known myocardial infarction or unstable angina within 6 months prior to randomization are also excluded.

  • QTc Fridericia (QTcF) > 470 ms. For patients with longer QTcF on initial electrocardiogram (ECG), follow-up ECG may be performed in triplicate to determine eligibility

  • Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0

  • Clinically significant interstitial lung disease

  • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen

  • Active hepatitis B or hepatitis C infection or infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] are eligible)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: ZW25 + FP

ZW25 plus fluorouracil (5-FU) and cisplatin
Legemiddel: Cisplatin

Administered IV

Legemiddel: ZW25 (Zanidatamab)
  • Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
  • Part 2: RD identified in Part 1
Legemiddel: Fluorouracil

Administered IV
Eksperimentell: ZW25 + mFOLFOX6

ZW25 plus 5-FU, leucovorin, and oxaliplatin
Legemiddel: Oxaliplatin

Administered IV

Legemiddel: ZW25 (Zanidatamab)
  • Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
  • Part 2: RD identified in Part 1
Legemiddel: Fluorouracil

Administered IV

Legemiddel: Leucovorin

Administered IV
Eksperimentell: ZW25 + XELOX

ZW25 plus capecitabine and oxaliplatin
Legemiddel: Oxaliplatin

Administered IV

Legemiddel: ZW25 (Zanidatamab)
  • Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
  • Part 2: RD identified in Part 1
Legemiddel: Capecitabine

Administered orally twice daily (PO bid)
Eksperimentell: ZW25 + mFOLFOX6 with bevacizumab

ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab
Legemiddel: Oxaliplatin

Administered IV

Legemiddel: Bevacizumab

Administered IV

Legemiddel: ZW25 (Zanidatamab)
  • Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
  • Part 2: RD identified in Part 1
Legemiddel: Fluorouracil

Administered IV

Legemiddel: Leucovorin

Administered IV
Eksperimentell: ZW25 + CisGem

ZW25 plus cisplatin and gemcitabine
Legemiddel: Cisplatin

Administered IV

Legemiddel: Gemcitabine

Administered IV

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Tidsramme: Cycle 1 of treatment for all Part 1 treatment regimens (each cycle is 21 days for the XELOX, FP, and CisGem regimens; 28 days for the mFOLFOX6 regimens)

DLTs include adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen.
Cycle 1 of treatment for all Part 1 treatment regimens (each cycle is 21 days for the XELOX, FP, and CisGem regimens; 28 days for the mFOLFOX6 regimens)
Number of Participants Reporting Treatment-emergent Adverse Events (Part 1; Parts 1 and 2)
Tidsramme: From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months

AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (v5.0).
From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months
Number of Participants Reporting Grade 3 or Higher Laboratory Abnormalities (Parts 1 and 2)
Tidsramme: From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months

Grades of laboratory abnormalities were defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months
Confirmed Objective Response Rate (ORR) (Parts 1 and 2)
Tidsramme: From time from confirmed best response (CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first, up to approximately 68 months

Number of participants who achieved a confirmed best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
From time from confirmed best response (CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first, up to approximately 68 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Disease Control Rate (Parts 1 and 2)
Tidsramme: From time from best response (CR, PR, SD) to documented PD per RECIST 1.1 or death from any cause, whichever occurred first, up to approximately 68 months

Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
From time from best response (CR, PR, SD) to documented PD per RECIST 1.1 or death from any cause, whichever occurred first, up to approximately 68 months
Duration of Response (Parts 1 and 2)
Tidsramme: From time from the first objective response (CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurred first, up to approximately 68 months

Median duration of response (in months) and range (minimum, maximum) are reported. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
From time from the first objective response (CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurred first, up to approximately 68 months
Clinical Benefit Rate (Parts 1 and 2)
Tidsramme: From time from the response (SD ≥ 24 weeks, CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first, up to approximately 68 months

Number of participants with SD for ≥ 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
From time from the response (SD ≥ 24 weeks, CR or PR) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first, up to approximately 68 months
Progression-free Survival (Parts 1 and 2)
Tidsramme: From the time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause, whichever occurred first, up to approximately 68 months

Median progression-free survival (in months) and range (minimum, maximum) are reported. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
From the time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause, whichever occurred first, up to approximately 68 months
Overall Survival (Parts 1 and 2)
Tidsramme: From the time from the date of first dose of study treatment until the date of death from any cause, up to approximately 68 months

Median overall survival (in months) and range (minimum, maximum) are reported. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
From the time from the date of first dose of study treatment until the date of death from any cause, up to approximately 68 months
Incidence of Postbaseline Anti-drug Antibodies (ADAs) (Parts 1 and 2)
Tidsramme: Cycle 1 Day 1 up to 30 days after last dose, up to approximately 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)

Number of participants who develop postbaseline ADAs are reported. Results are presented separately for the GEA and BTC cancer groups based on Parts 1 and 2 combined and for the CRC cancer group based on Part 1 only.
Cycle 1 Day 1 up to 30 days after last dose, up to approximately 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)
End of Infusion Concentration of ZW25 (Parts 1 and 2)
Tidsramme: Cycle 1 predose up to end of treatment, up to 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)

Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Cycle 1 predose up to end of treatment, up to 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)
Maximum Serum Concentration of ZW25 (Parts 1 and 2)
Tidsramme: Cycle 1 predose up to end of treatment, up to 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)

Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Cycle 1 predose up to end of treatment, up to 68 months (for ZW25 combined with XELOX, FP, or CisGem, each treatment cycle is 21 days; for ZW25 in combination with FOLFOX6 with or without bevacizumab, each treatment cycle is 28 days)
Trough Concentration of ZW25 (Parts 1 and 2)
Tidsramme: Cycle 1, Day 15; Cycle 2, Days 1 and 15; Cycle 3, Days 1 and 15; Cycle 4, Day 1, and Cycle 6, Day 1 (for ZW25 combined with XELOX, FP, or CisGem, each cycle is 21 days; for ZW25 combined with FOLFOX6 with or without BEV, each cycle is 28 days)

Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Cycle 1, Day 15; Cycle 2, Days 1 and 15; Cycle 3, Days 1 and 15; Cycle 4, Day 1, and Cycle 6, Day 1 (for ZW25 combined with XELOX, FP, or CisGem, each cycle is 21 days; for ZW25 combined with FOLFOX6 with or without BEV, each cycle is 28 days)
Number of Participants Reporting Treatment-emergent Adverse Events (Part 1; Parts 1 and 2)
Tidsramme: From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months.

Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (v5.0).
From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months.
Number of Participants Reporting Grade 3 or Higher Laboratory Abnormalities (Parts 1 and 2)
Tidsramme: From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months.

Number of participants who experienced a maximum severity of Grade 3 or higher postbaseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
From the start of dosing of any study drug through 30 days after last study treatment or prior to beginning the next course of anticancer therapy, whichever occurs sooner, up to approximately 68 months.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Jazz Pharmaceuticals

Etterforskere

  • Studieleder: Jazz Medical Director, Jazz Pharmaceuticals

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

22. august 2019

Primær fullføring (Faktiske)

30. august 2025

Studiet fullført (Faktiske)

30. august 2025

Datoer for studieregistrering

Først innsendt

22. februar 2019

Først innsendt som oppfylte QC-kriteriene

23. april 2019

Først lagt ut (Faktiske)

29. april 2019

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

4. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

13. oktober 2026

Sist bekreftet

1. oktober 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ZWI-ZW25-201

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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