A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer
- Conditions
- HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer
- Interventions
- Registration Number
- NCT03929666
- Lead Sponsor
- Jazz Pharmaceuticals
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 74
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ZW25 + FP ZW25 (Zanidatamab) ZW25 plus fluorouracil (5-FU) and cisplatin ZW25 + FP Cisplatin ZW25 plus fluorouracil (5-FU) and cisplatin ZW25 + mFOLFOX6 Oxaliplatin ZW25 plus 5-FU, leucovorin, and oxaliplatin ZW25 + mFOLFOX6 with bevacizumab ZW25 (Zanidatamab) ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab ZW25 + XELOX ZW25 (Zanidatamab) ZW25 plus capecitabine and oxaliplatin ZW25 + mFOLFOX6 ZW25 (Zanidatamab) ZW25 plus 5-FU, leucovorin, and oxaliplatin ZW25 + mFOLFOX6 with bevacizumab Bevacizumab ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab ZW25 + FP Fluorouracil ZW25 plus fluorouracil (5-FU) and cisplatin ZW25 + mFOLFOX6 Fluorouracil ZW25 plus 5-FU, leucovorin, and oxaliplatin ZW25 + mFOLFOX6 Leucovorin ZW25 plus 5-FU, leucovorin, and oxaliplatin ZW25 + XELOX Capecitabine ZW25 plus capecitabine and oxaliplatin ZW25 + mFOLFOX6 with bevacizumab Oxaliplatin ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab ZW25 + mFOLFOX6 with bevacizumab Fluorouracil ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab ZW25 + XELOX Oxaliplatin ZW25 plus capecitabine and oxaliplatin ZW25 + mFOLFOX6 with bevacizumab Leucovorin ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab ZW25 + CisGem Cisplatin ZW25 plus cisplatin and gemcitabine ZW25 + CisGem Gemcitabine ZW25 plus cisplatin and gemcitabine
- Primary Outcome Measures
Name Time Method Incidence of adverse events (Part 1) Up to 11 months Number of participants who experienced an adverse event
Objective response rate (ORR) (Part 2) Up to 10 months Number of participants who achieved a 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
Incidence of dose-limiting toxicities (DLTs) (Part 1) Up to 6 weeks Number of participants who experienced a DLT. 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.
Incidence of lab abnormalities (Part 1) Up to 11 months Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Secondary Outcome Measures
Name Time Method Overall survival (Parts 1 and 2) Up to 2 years Median overall survival (in months) and range (minimum, maximum)
Duration of response (Parts 1 and 2) Up to 2 years Median duration of response (in months) and range (minimum, maximum)
Trough concentration of ZW25 (Parts 1 and 2) Up to 11 months Incidence of adverse events (Part 2) Up to 11 months Number of participants who experienced an adverse event
Incidence of lab abnormalities (Part 2) Up to 11 months Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0.
Objective response rate (ORR) (Part 1) Up to 10 months Number of participants who achieved a best response of either CR or PR during treatment per RECIST 1.1
Disease control rate (Parts 1 and 2) Up to 10 months Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
Clinical benefit rate (Parts 1 and 2) Up to 2 years Number of participants with SD for ≥ 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1
Progression-free survival (Parts 1 and 2) Up to 2 years Median progression-free survival (in months) and range (minimum, maximum)
Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) Up to 11 months Number of participants who develop ADAs
End of infusion concentration of ZW25 (Parts 1 and 2) Up to 11 months Maximum serum concentration of ZW25 (Parts 1 and 2) Up to 11 months
Trial Locations
- Locations (23)
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
The Cancer and Hematology Centers
🇺🇸Grand Rapids, Michigan, United States
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Centro de Investigacion Clinica SAGA
🇨🇱Santiago, Chile
Centro Internacional de Estudios Clínicos
🇨🇱Santiago, Chile
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Icegclinic Research & Care
🇨🇱Santiago, Chile
CECIM Biocinetic
🇨🇱Santiago, Chile
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Pusan National University
🇰🇷Busan, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of