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Studie bezpečnosti a účinnosti kombinované chemoterapie ZW25 (Zanidatamab) Plus u karcinomů trávicího traktu exprimujících HER2, včetně adenokarcinomu gastroezofageálního karcinomu, rakoviny žlučových cest a kolorektálního karcinomu

13. října 2026 aktualizováno: Jazz Pharmaceuticals

Studie fáze 2 kombinované chemoterapie ZW25 Plus první linie u karcinomů gastrointestinálního traktu (GI) exprimujících HER2, včetně adenokarcinomu jícnu (GEA), rakoviny žlučových cest (BTC) a kolorektálního karcinomu (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).

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

74

Fáze

  • Fáze 2

Rozšířený přístup

Již není k dispozici mimo klinické hodnocení. Viz rozšířený záznam o přístupu.

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • 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
  • Jižní Korea
      • Busan, Jižní Korea, 49241
        • Pusan National University
      • Seoul, Jižní Korea, 03080
        • Seoul National University Hospital
      • Seoul, Jižní Korea, 05505
        • Asan Medical Center
      • Seoul, Jižní Korea, 03722
        • Severance Hospital
      • Seoul, Jižní Korea, 02841
        • Korea University Anam Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Jižní Korea, 13620
        • Seoul National University Bundang Hospital
  • Kanada
    • Ontario
      • Ottawa, Ontario, Kanada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Kanada, M5G 2C1
        • Princess Margaret Cancer Center
  • Spojené státy
    • California
      • Los Angeles, California, Spojené státy, 90033
        • USC/Norris Comprehensive Cancer Center
      • Newport Beach, California, Spojené státy, 92663
        • Hoag Memorial Hospital Presbyterian
    • Florida
      • Tampa, Florida, Spojené státy, 33612
        • H. Lee Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, Spojené státy, 60637
        • University of Chicago
    • Michigan
      • Grand Rapids, Michigan, Spojené státy, 49503
        • The Cancer and Hematology Centers
    • Nebraska
      • Omaha, Nebraska, Spojené státy, 68114
        • Nebraska Methodist Hospital
    • New York
      • New York, New York, Spojené státy, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Spojené státy, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, Spojené státy, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, Spojené státy, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Spojené státy, 98101
        • Virginia Mason Medical Center

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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)

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Nerandomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: ZW25 + FP

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

Administered IV

Lék: 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
Lék: Fluorouracil

Administered IV
Experimentální: ZW25 + mFOLFOX6

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

Administered IV

Lék: 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
Lék: Fluorouracil

Administered IV

Lék: Leucovorin

Administered IV
Experimentální: ZW25 + XELOX

ZW25 plus capecitabine and oxaliplatin
Lék: Oxaliplatin

Administered IV

Lék: 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
Lék: Capecitabine

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

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

Administered IV

Lék: Bevacizumab

Administered IV

Lék: 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
Lék: Fluorouracil

Administered IV

Lék: Leucovorin

Administered IV
Experimentální: ZW25 + CisGem

ZW25 plus cisplatin and gemcitabine
Lék: Cisplatin

Administered IV

Lék: Gemcitabine

Administered IV

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Disease Control Rate (Parts 1 and 2)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Jazz Pharmaceuticals

Vyšetřovatelé

  • Ředitel studie: Jazz Medical Director, Jazz Pharmaceuticals

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

22. srpna 2019

Primární dokončení (Aktuální)

30. srpna 2025

Dokončení studie (Aktuální)

30. srpna 2025

Termíny zápisu do studia

První předloženo

22. února 2019

První předloženo, které splnilo kritéria kontroly kvality

23. dubna 2019

První zveřejněno (Aktuální)

29. dubna 2019

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

4. listopadu 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

13. října 2026

Naposledy ověřeno

1. října 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • ZWI-ZW25-201

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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