Um estudo de segurança e eficácia da quimioterapia combinada ZW25 (Zanidatamab) Plus em cânceres gastrointestinais que expressam HER2, incluindo adenocarcinoma gastroesofágico, câncer do trato biliar e câncer colorretal
Estudo de fase 2 da quimioterapia combinada de primeira linha ZW25 Plus em cânceres gastrointestinais (GI) que expressam HER2, incluindo adenocarcinoma gastroesofágico (GEA), câncer do trato biliar (BTC) e câncer colorretal (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).
Visão geral do estudo
Status
Descrição detalhada
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 de estudo
Inscrição (Real)
Estágio
- Fase 2
Acesso expandido
Contactos e Locais
Locais de estudo
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Ontario
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Ottawa, Ontario, Canadá, K1H 8L6
- The Ottawa Hospital Cancer Centre
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Toronto, Ontario, Canadá, M5G 2C1
- Princess Margaret Cancer Center
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Santiago, Chile, 8241479
- Icegclinic Research & Care
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Santiago, Chile, 8420383
- Centro Internacional de Estudios Clínicos
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Santiago, Chile, 7500653
- Centro de Investigacion Clinica SAGA
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Santiago, Chile, 8320000
- CECIM Biocinetic
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Busan, Coréia do Sul, 49241
- Pusan National University
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Seoul, Coréia do Sul, 03080
- Seoul National University Hospital
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Seoul, Coréia do Sul, 05505
- Asan Medical Center
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Seoul, Coréia do Sul, 03722
- Severance Hospital
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Seoul, Coréia do Sul, 02841
- Korea University Anam Hospital
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Gyeonggi-do
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Seongnam-si, Gyeonggi-do, Coréia do Sul, 13620
- Seoul National University Bundang Hospital
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California
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Los Angeles, California, Estados Unidos, 90033
- USC/Norris Comprehensive Cancer Center
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Newport Beach, California, Estados Unidos, 92663
- Hoag Memorial Hospital Presbyterian
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Florida
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Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago
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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- The Cancer and Hematology Centers
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68114
- Nebraska Methodist Hospital
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New York
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19111
- Fox Chase Cancer Center
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Sarah Cannon Research Institute
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Texas
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Houston, Texas, Estados Unidos, 77030
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, Estados Unidos, 98101
- Virginia Mason Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion:
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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
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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
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An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
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Adequate organ function
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Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal
Exclusion:
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Prior treatment with a HER2-targeted agent
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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).
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Patients with certain contraindications to bevacizumab cannot be enrolled on the mFOLFOX6-2 with bevacizumab arm.
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Palliative radiotherapy is allowed if completed at least 2 weeks prior to first study treatment dosing
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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)
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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.
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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
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Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0
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Clinically significant interstitial lung disease
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Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
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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)
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: ZW25 + FP
ZW25 plus fluorouracil (5-FU) and cisplatin |
Administered IV
Administered IV |
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Experimental: ZW25 + mFOLFOX6
ZW25 plus 5-FU, leucovorin, and oxaliplatin |
Administered IV
Administered IV Administered IV |
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Experimental: ZW25 + XELOX
ZW25 plus capecitabine and oxaliplatin |
Administered IV
Administered orally twice daily (PO bid) |
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Experimental: ZW25 + mFOLFOX6 with bevacizumab
ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab |
Administered IV Administered IV
Administered IV Administered IV |
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Experimental: ZW25 + CisGem
ZW25 plus cisplatin and gemcitabine |
Administered IV Administered IV |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Prazo: 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)
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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)
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Number of Participants Reporting Treatment-emergent Adverse Events (Part 1; Parts 1 and 2)
Prazo: 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
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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
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Number of Participants Reporting Grade 3 or Higher Laboratory Abnormalities (Parts 1 and 2)
Prazo: 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
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Confirmed Objective Response Rate (ORR) (Parts 1 and 2)
Prazo: 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
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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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Disease Control Rate (Parts 1 and 2)
Prazo: 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
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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
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Duration of Response (Parts 1 and 2)
Prazo: 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
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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
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Clinical Benefit Rate (Parts 1 and 2)
Prazo: 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
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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
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Progression-free Survival (Parts 1 and 2)
Prazo: 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
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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
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Overall Survival (Parts 1 and 2)
Prazo: 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
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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
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Incidence of Postbaseline Anti-drug Antibodies (ADAs) (Parts 1 and 2)
Prazo: 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)
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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)
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End of Infusion Concentration of ZW25 (Parts 1 and 2)
Prazo: 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)
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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)
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Maximum Serum Concentration of ZW25 (Parts 1 and 2)
Prazo: 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)
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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)
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Trough Concentration of ZW25 (Parts 1 and 2)
Prazo: 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)
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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)
|
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Number of Participants Reporting Treatment-emergent Adverse Events (Part 1; Parts 1 and 2)
Prazo: 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)
Prazo: 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.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Jazz Medical Director, Jazz Pharmaceuticals
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
- Capecitabina
- Câncer colorretal
- HER2
- Imunoterapia
- Cisplatina
- Quimioterapia
- Colangiocarcinoma extra-hepático
- Oxaliplatina
- 5-FU
- Anticorpo biespecífico
- Anticorpo biparatópico
- Câncer de vias biliares
- XELOX
- PF
- Colangiocarcinoma intra-hepático
- Adenocarcinoma gastroesofágico
- Cânceres gástricos
- Cânceres de esôfago
- Vesícula biliar
- Tumores da junção gastroesofágica (GEJ)
- mFOLFOX6
- Leucovorina (ácido folínico)
- Cânceres gastrointestinais
Termos MeSH relevantes adicionais
- Neoplasias por local
- Doenças Intestinais
- Neoplasias por Tipo Histológico
- Neoplasias do Aparelho Digestivo
- Doenças do aparelho digestivo
- Doenças Gastrointestinais
- Doenças do Estômago
- Neoplasias Intestinais
- Doenças retais
- Neoplasias de Cabeça e Pescoço
- Doenças das vias biliares
- Neoplasias Glandulares e Epiteliais
- Adenocarcinoma
- Doenças do cólon
- Doenças Esofágicas
- Carcinoma
- Neoplasias
- Neoplasias do Estômago
- Neoplasias das Vias Biliares
- Neoplasias Colorretais
- Neoplasias Esofágicas
- Neoplasias gastrointestinais
- Colangiocarcinoma
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Ácidos nucleicos, nucleotídeos e nucleosídeos
- Enzimas e coenzimas
- Anticorpos, monoclonais, humanizados
- Anticorpos, monoclonais
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Produtos químicos inorgânicos
- Compostos de cloro
- Compostos de nitrogênio
- Complexos de coordenação
- Desoxicitidina
- Citidina
- Nucleosídeos de pirimidina
- Pirimidinas
- Nucleosídeos
- Formiltetra -hidrofolatos
- Tetra -hidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracil
- Pirimidinonas
- Coenzimas
- Compostos de platina
- Desoxirribonucleosídeos
- Capecitabina
- Oxaliplatina
- Bevacizumabe
- Gemcitabina
- Fluorouracila
- Leucovorina
- Cisplatina
- Zanidatamab
Outros números de identificação do estudo
- ZWI-ZW25-201
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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