HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal CancerPhase 2NCT03929666
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
A Phase 2 study testing ZW25 (Zanidatamab), Capecitabine and Cisplatin in people with HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer, run by Jazz Pharmaceuticals at 23 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer
- What is being tested?
- ZW25 (Zanidatamab), Capecitabine and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 23 sitesin 4 countries
- Study dates
- 22 Aug 2019to 30 Aug 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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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)
- 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)
Trial locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
United States11 sites
University of Chicago
Chicago, Illinois, 60637
The Cancer and Hematology Centers
Grand Rapids, Michigan, 49503
MD Anderson Cancer Center
Houston, Texas, 77030
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Virginia Mason Medical Center
Seattle, Washington, 98101
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
South Korea6 sites
Pusan National University
Busan, 49241
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Asan Medical Center
Seoul, 05505
Chile4 sites
Centro de Investigacion Clinica SAGA
Santiago, 7500653
Icegclinic Research & Care
Santiago, 8241479
CECIM Biocinetic
Santiago, 8320000
Centro Internacional de Estudios Clínicos
Santiago, 8420383
Canada2 sites
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2C1
About this study
Official title: Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastrointestinal (GI) Cancers, Including Gastroesophageal Adenocarcinoma (GEA), Biliary Tract Cancer (BTC), and Colorectal Cancer (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).
Read the 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.
- Being tested
- ZW25 (Zanidatamab), Capecitabine, Cisplatin, Fluorouracil, Leucovorin
- Keywords
- HER2, Bispecific antibody, Biparatopic antibody, Immunotherapy, Gastric cancers, Esophageal cancers, Gastroesophageal junction (GEJ) cancers, Chemotherapy, FP, mFOLFOX6, Capecitabine, Cisplatin, 5-FU, Leucovorin (folinic acid), Oxaliplatin, XELOX, Gastrointestinal cancers, Gastroesophageal adenocarcinoma, Biliary tract cancer, Colorectal cancer
- Medical subject headings
- Biliary Tract Neoplasms, Colorectal Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Neoplasms, Gastrointestinal Neoplasms, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZW25 (Zanidatamab)Drug
- Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
- Part 2: RD identified in Part 1
CapecitabineDrug
Administered orally twice daily (PO bid)
CisplatinDrug
Administered IV
FluorouracilDrug
Administered IV
LeucovorinDrug
Administered IV
OxaliplatinDrug
Administered IV
BevacizumabDrug
Administered IV
GemcitabineDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| ZW25 + FP | Experimental | ZW25 plus fluorouracil (5-FU) and cisplatin Receives: Drug: ZW25 (Zanidatamab); Drug: Cisplatin; Drug: Fluorouracil |
| ZW25 + mFOLFOX6 | Experimental | ZW25 plus 5-FU, leucovorin, and oxaliplatin Receives: Drug: ZW25 (Zanidatamab); Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin |
| ZW25 + XELOX | Experimental | ZW25 plus capecitabine and oxaliplatin Receives: Drug: ZW25 (Zanidatamab); Drug: Capecitabine; Drug: Oxaliplatin |
| ZW25 + mFOLFOX6 with bevacizumab | Experimental | ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab Receives: Drug: ZW25 (Zanidatamab); Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Bevacizumab |
| ZW25 + CisGem | Experimental | ZW25 plus cisplatin and gemcitabine Receives: Drug: Cisplatin; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
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.
Measured: 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)
AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (v5.0).
Measured: 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)
Grades of laboratory abnormalities were defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Measured: 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)
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
Measured: 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
Secondary outcomes (11)
Disease Control Rate (Parts 1 and 2)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Measured: 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)
Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Measured: 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)
Pharmacokinetic (PK) parameters were assessed using noncompartmental procedures.
Measured: 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)
Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (v5.0).
Measured: 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)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2019
- Study start22 Aug 2019
- Primary completion30 Aug 2025
- Study completion30 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jazz Medical Director, Study director, Jazz Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03929666
- Sponsor's protocol ID
- ZWI-ZW25-201
- Status last verified
- Oct 2026
- First submitted
- 22 Feb 2019
- Last updated
- 4 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Elimova E, Ajani J, Burris H, Denlinger CS, Iqbal S, Kang YK, Kim JH, Lee KW, Lin B, Mehta R, Oh DY, Rha SY, Seol YM, Yang L, Ozog MA, Garfin PM, Ku G. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol. 2025 Jul;26(7):847-859. doi: 10.1016/S1470-2045(25)00287-6. Epub 2025 Jun 2.
PubMed 40473445
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastrointestinal (GI) Cancers, Including Gastroesophageal Adenocarcinoma (GEA), Biliary Tract Cancer (BTC), and Colorectal Cancer (CRC)
- ClinicalTrials.gov ID
- NCT03929666
- Acronym / sponsor ID
- ZWI-ZW25-201
- Keywords
- HER2, Bispecific antibody, Biparatopic antibody, Immunotherapy, Gastric cancers, Esophageal cancers, Gastroesophageal junction (GEJ) cancers, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 Aug 2019 (actual)
- Primary completion
- 30 Aug 2025 (actual)
- Study completion
- 30 Aug 2025 (actual)
- First posted
- 29 Apr 2019 (actual)
- Results
- Posted 4 Nov 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| ZW25 + FP | Experimental | Drug: ZW25 (Zanidatamab), Drug: Cisplatin, Drug: FluorouracilZW25 plus fluorouracil (5-FU) and cisplatin |
| ZW25 + mFOLFOX6 | Experimental | Drug: ZW25 (Zanidatamab), Drug: Fluorouracil, Drug: Leucovorin, Drug: OxaliplatinZW25 plus 5-FU, leucovorin, and oxaliplatin |
| ZW25 + XELOX | Experimental | Drug: ZW25 (Zanidatamab), Drug: Capecitabine, Drug: OxaliplatinZW25 plus capecitabine and oxaliplatin |
| ZW25 + mFOLFOX6 with bevacizumab | Experimental | Drug: ZW25 (Zanidatamab), Drug: Fluorouracil, Drug: Leucovorin, Drug: Oxaliplatin, Drug: BevacizumabZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab |
| ZW25 + CisGem | Experimental | Drug: Cisplatin, Drug: GemcitabineZW25 plus cisplatin and gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Disease diagnosis:
- Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1:
- 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
Key exclusion criteria (13 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | ZW25 + FP, ZW25 + XELOX, ZW25 + mFOLFOX6, ZW25 + mFOLFOX6 with bevacizumab |
| CapecitabineAdministered orally twice daily (PO bid) | Drug | ZW25 + XELOX |
| CisplatinAdministered IV | Drug | ZW25 + CisGem, ZW25 + FP |
| FluorouracilAdministered IV | Drug | ZW25 + FP, ZW25 + mFOLFOX6, ZW25 + mFOLFOX6 with bevacizumab |
| LeucovorinAdministered IV | Drug | ZW25 + mFOLFOX6, ZW25 + mFOLFOX6 with bevacizumab |
| OxaliplatinAdministered IV | Drug | ZW25 + XELOX, ZW25 + mFOLFOX6, ZW25 + mFOLFOX6 with bevacizumab |
| BevacizumabAdministered IV | Drug | ZW25 + mFOLFOX6 with bevacizumab |
| GemcitabineAdministered IV | Drug | ZW25 + CisGem |
Primary outcome
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1)
Time frame: 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.
Number of Participants Reporting Treatment-emergent Adverse Events (Part 1; Parts 1 and 2)
Time frame: 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).
Number of Participants Reporting Grade 3 or Higher Laboratory Abnormalities (Parts 1 and 2)
Time frame: 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.
Confirmed Objective Response Rate (ORR) (Parts 1 and 2)
Time frame: 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
11 secondary outcomes
Disease Control Rate (Parts 1 and 2)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40473445Elimova E, Ajani J, Burris H, Denlinger CS, Iqbal S, Kang YK, Kim JH, Lee KW, Lin B, Mehta R, Oh DY, Rha SY, Seol YM, Yang L, Ozog MA, Garfin PM, Ku G. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol. 2025 Jul;26(7):847-859. doi: 10.1016/S1470-2045(25)00287-6. Epub 2025 Jun 2.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jazz Medical Director study director
Jazz Pharmaceuticals
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZW25 (Zanidatamab), Capecitabine and Cisplatin in people with HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer, run by Jazz Pharmaceuticals at 23 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, South Korea, Chile, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting Dose-limiting Toxicities (DLTs) (Part 1) (time frame: 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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03929666, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.