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Исследование безопасности и эффективности ZW25 (занидатамаб) плюс комбинированная химиотерапия при HER2-экспрессирующем раке желудочно-кишечного тракта, включая гастроэзофагеальную аденокарциному, рак желчных путей и колоректальный рак

13 октября 2026 г. обновлено: Jazz Pharmaceuticals

Фаза 2 исследования комбинированной химиотерапии ZW25 Plus первой линии при HER2-экспрессирующем раке желудочно-кишечного тракта (ЖКТ), включая гастроэзофагеальную аденокарциному (GEA), рак желчных путей (BTC) и колоректальный рак (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).

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

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.

Тип исследования

Интервенционный

Регистрация (Действительный)

74

Фаза

  • Фаза 2

Расширенный доступ

Больше недоступно вне клинических испытаний. См. запись расширенного доступа.

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

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

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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)

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Нерандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: ZW25 + FP

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

Administered IV

Лекарство: 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
Лекарство: Fluorouracil

Administered IV
Экспериментальный: ZW25 + mFOLFOX6

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

Administered IV

Лекарство: 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
Лекарство: Fluorouracil

Administered IV

Лекарство: Leucovorin

Administered IV
Экспериментальный: ZW25 + XELOX

ZW25 plus capecitabine and oxaliplatin
Лекарство: Oxaliplatin

Administered IV

Лекарство: 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
Лекарство: Capecitabine

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

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

Administered IV

Лекарство: Bevacizumab

Administered IV

Лекарство: 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
Лекарство: Fluorouracil

Administered IV

Лекарство: Leucovorin

Administered IV
Экспериментальный: ZW25 + CisGem

ZW25 plus cisplatin and gemcitabine
Лекарство: Cisplatin

Administered IV

Лекарство: Gemcitabine

Administered IV

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Disease Control Rate (Parts 1 and 2)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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.

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Jazz Pharmaceuticals

Следователи

  • Директор по исследованиям: Jazz Medical Director, Jazz Pharmaceuticals

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

22 августа 2019 г.

Первичное завершение (Действительный)

30 августа 2025 г.

Завершение исследования (Действительный)

30 августа 2025 г.

Даты регистрации исследования

Первый отправленный

22 февраля 2019 г.

Впервые представлено, что соответствует критериям контроля качества

23 апреля 2019 г.

Первый опубликованный (Действительный)

29 апреля 2019 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

4 ноября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

13 октября 2026 г.

Последняя проверка

1 октября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • ZWI-ZW25-201

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕТ

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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