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Uno studio sulla sicurezza e l'efficacia di ZW25 (Zanidatamab) più chemioterapia combinata nei tumori gastrointestinali che esprimono HER2, tra cui l'adenocarcinoma gastroesofageo, il cancro delle vie biliari e il cancro del colon-retto

13 ottobre 2026 aggiornato da: Jazz Pharmaceuticals

Studio di fase 2 sulla chemioterapia combinata di prima linea ZW25 Plus nei tumori gastrointestinali (GI) che esprimono HER2, tra cui l'adenocarcinoma gastroesofageo (GEA), il cancro del tratto biliare (BTC) e il cancro del colon-retto (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).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

74

Fase

  • Fase 2

Accesso esteso

Non più disponibile al di fuori della sperimentazione clinica. Vedi record di accesso esteso.

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • 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
  • Corea del Sud
      • Busan, Corea del Sud, 49241
        • Pusan National University
      • Seoul, Corea del Sud, 03080
        • Seoul National University Hospital
      • Seoul, Corea del Sud, 05505
        • Asan Medical Center
      • Seoul, Corea del Sud, 03722
        • Severance Hospital
      • Seoul, Corea del Sud, 02841
        • Korea University Anam Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Corea del Sud, 13620
        • Seoul National University Bundang Hospital
  • Stati Uniti
    • California
      • Los Angeles, California, Stati Uniti, 90033
        • USC/Norris Comprehensive Cancer Center
      • Newport Beach, California, Stati Uniti, 92663
        • Hoag Memorial Hospital Presbyterian
    • Florida
      • Tampa, Florida, Stati Uniti, 33612
        • H. Lee Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60637
        • University of Chicago
    • Michigan
      • Grand Rapids, Michigan, Stati Uniti, 49503
        • The Cancer and Hematology Centers
    • Nebraska
      • Omaha, Nebraska, Stati Uniti, 68114
        • Nebraska Methodist Hospital
    • New York
      • New York, New York, Stati Uniti, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, Stati Uniti, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Stati Uniti, 98101
        • Virginia Mason Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: ZW25 + FP

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

Administered IV

Droga: 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
Droga: Fluorouracil

Administered IV
Sperimentale: ZW25 + mFOLFOX6

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

Administered IV

Droga: 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
Droga: Fluorouracil

Administered IV

Droga: Leucovorin

Administered IV
Sperimentale: ZW25 + XELOX

ZW25 plus capecitabine and oxaliplatin
Droga: Oxaliplatin

Administered IV

Droga: 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
Droga: Capecitabine

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

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

Administered IV

Droga: Bevacizumab

Administered IV

Droga: 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
Droga: Fluorouracil

Administered IV

Droga: Leucovorin

Administered IV
Sperimentale: ZW25 + CisGem

ZW25 plus cisplatin and gemcitabine
Droga: Cisplatin

Administered IV

Droga: Gemcitabine

Administered IV

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Disease Control Rate (Parts 1 and 2)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Jazz Pharmaceuticals

Investigatori

  • Direttore dello studio: Jazz Medical Director, Jazz Pharmaceuticals

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

22 agosto 2019

Completamento primario (Effettivo)

30 agosto 2025

Completamento dello studio (Effettivo)

30 agosto 2025

Date di iscrizione allo studio

Primo inviato

22 febbraio 2019

Primo inviato che soddisfa i criteri di controllo qualità

23 aprile 2019

Primo Inserito (Effettivo)

29 aprile 2019

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

4 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • ZWI-ZW25-201

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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