Esophageal Cancer Clinical Trial

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

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).

View Full Description

Full 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.

View Eligibility Criteria

Eligibility Criteria

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)

Study is for people with:

Esophageal Cancer

Phase:

Phase 2

Estimated Enrollment:

362

Study ID:

NCT03929666

Recruitment Status:

Recruiting

Sponsor:

Zymeworks Inc.

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 20 Locations for this study

See Locations Near You

USC/Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States More Info
Syma Iqbal, MD
Principal Investigator
H. Lee Moffitt Cancer Center
Tampa Florida, 33612, United States
Cancer and Hematology Centers of Western Michigan
Kalamazoo Michigan, 49007, United States More Info
Sreenivasa Chandana, MD
Principal Investigator
Nebraska Methodist Hospital
Omaha Nebraska, 68114, United States More Info
Joel Michalski, MD
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Geoffrey Ku, MD
Principal Investigator
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States
Sarah Cannon Research Institute
Nashville Tennessee, 37203, United States More Info
Howard Burris, MD
Principal Investigator
MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Jaffer Ajani, MD
Principal Investigator
Virginia Mason Medical Center
Seattle Washington, 98101, United States More Info
Bruce Lin, MD
Principal Investigator
Princess Margaret Cancer Center
Toronto Ontario, M5G 2, Canada More Info
Elena Elimova, MD
Principal Investigator
Centro de Estudios Clinicos SAGA SpA
Santiago , 75006, Chile More Info
Marcelo Adán Garrido Salvo, MD
Principal Investigator
Icegclinic Research & Care
Santiago , 82414, Chile More Info
Anrried Mariana Escalante Sorrentino, MD
Principal Investigator
Meditek Ltda
Santiago , 83300, Chile More Info
Ernesto Antonio Maturana Leiva, MD
Principal Investigator
CECIM Biocinetic
Santiago , 83311, Chile More Info
Marco Bernaschina Olivares, MD
Principal Investigator
Seoul National University Bundang Hospital
Seongnam-si Gyeonggi-do, 13620, Korea, Republic of More Info
Keun-Wook Lee, MD, PhD
Principal Investigator
Pusan National University
Busan , 49241, Korea, Republic of More Info
Young Mi Seol, MD, PhD
Principal Investigator
Korea University Anam Hospital
Seoul , 02841, Korea, Republic of More Info
Yeul Hong Kim, MD, PhD
Principal Investigator
Seoul National University Hospital
Seoul , 03080, Korea, Republic of More Info
Do-Youn Oh, MD, PhD
Principal Investigator
Severance Hospital
Seoul , 03722, Korea, Republic of More Info
Sun Young Rha, MD, PhD
Principal Investigator
Asan Medical Center
Seoul , 05505, Korea, Republic of More Info
Yoon-Koo Kang, MD, PhD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Esophageal Cancer

Phase:

Phase 2

Estimated Enrollment:

362

Study ID:

NCT03929666

Recruitment Status:

Recruiting

Sponsor:


Zymeworks Inc.

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.