Study of Zanidatamab and Tislelizumab Combined with Chemotherapy for Patients with Advanced or Metastatic HER2-positive Gastroesophageal Cancer

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What is this study about?

This study focuses on patients with HER2-positive Gastroesophageal Adenocarcinoma, which is a type of cancer affecting the stomach and esophagus (the tube connecting the mouth to the stomach) that cannot be removed by surgery or has spread to other parts of the body. The study tests a combination of medications including zanidatamab (also known as JZP598), tislelizumab, and standard chemotherapy drugs including capecitabine. These are compared to treatment with trastuzumab (a currently approved therapy) combined with chemotherapy.

The purpose of this research is to determine if using zanidatamab with chemotherapy, either alone or together with tislelizumab, works better than the current standard treatment of trastuzumab with chemotherapy. Zanidatamab and tislelizumab are new medications that work by helping the body’s immune system fight cancer cells. During treatment, patients may also receive loperamide, a medication that helps control diarrhea which can occur as a side effect of treatment.

Participants in this study will be randomly assigned to receive either the new treatment combination or the standard treatment. The medications will be given through an intravenous infusion (delivered directly into a vein), while some medications will be taken by mouth. The study treatment may continue for up to 756 days, depending on how well it works and how well it is tolerated by patients.

1 Initial assessment

Your doctor will perform tests to confirm HER2-positive gastroesophageal cancer that cannot be removed by surgery or has spread to other parts of the body

A heart test will be done to check if your heart function (LVEF) is at least 50%

Your overall physical condition will be evaluated using a scale called ECOG, which must show a score of 0 or 1

2 Assignment to treatment group

You will be randomly assigned to one of the treatment groups

Each group receives different combinations of medications through infusion and oral tablets

3 Treatment administration

You will receive treatment with one of these combinations:

– Zanidatamab (given by intravenous infusion) with chemotherapy

– Zanidatamab with chemotherapy plus tislelizumab (both given by intravenous infusion)

– Trastuzumab (given by intravenous infusion) with chemotherapy

Capecitabine will be given as oral tablets as part of the chemotherapy

Loperamide may be provided as oral medication if needed

4 Monitoring and evaluation

Regular scans will be performed to measure how the cancer responds to treatment

Your health status and any side effects will be monitored throughout the study

Quality of life questionnaires will need to be completed periodically

Blood samples will be taken to measure medication levels in your body

5 Follow-up period

After completing treatment, you will continue to be monitored to assess long-term results

The study is expected to continue until June 2027

Who Can Join the Study?

Must have confirmed gastroesophageal adenocarcinoma (cancer of the stomach or esophagus) that is:
- Cannot be surgically removed (unresectable)
- Locally advanced
- Recurrent, or
- Has spread to other parts of the body (metastatic)
Cancer must be HER2-positive, confirmed by specific laboratory tests (IHC 3+ or IHC 2+ with ISH positive)
Must have disease that can be measured or assessed by medical imaging
Must have good physical functioning ability (ECOG performance status of 0 or 1)
Must have adequate organ function
Must have good heart function with left ventricular ejection fraction (heart pumping ability) of 50% or higher
Can be either male or female
Must be an adult (18 years or older)

Who Cannot Join the Study?

Patients with unresectable locally advanced, recurrent or metastatic HER2 negative gastric cancer
Previous treatment with zanidatamab or tislelizumab (these are the study medications)
History of other cancers within the last 5 years, except for successfully treated non-melanoma skin cancer or cervical cancer in situ
Severe heart conditions, including:
- Uncontrolled high blood pressure
- Unstable heart disease
- Heart attack within the past 6 months
Active or untreated brain metastases (cancer that has spread to the brain)
Serious infections requiring treatment, including active tuberculosis or hepatitis B
Known allergic reactions to the study medications or similar drugs
Participation in another clinical trial within 30 days before starting this study
Pregnancy or breastfeeding
Unable to swallow oral medications
Any condition that, in the opinion of the study doctor, would make participation unsafe

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centr Georges Francois Leclerc	Dijon	France
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Hospital Universitario De Navarra	Pamplona	Spain
Medisprof S.R.L.	Cluj Napoca	Romania
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France
Oncopole Claudius Regaud	Toulouse	France
Katholieke Universiteit te Leuven	Leuven	Belgium
Comite Entreprise Paul Papin	Angers	France

Other Sites

Site Name	City	Country
Krankenhaus Nordwest GmbH	Frankfurt	Germany
Centre Hospitalier Universitaire De Poitiers	Poitiers	France
Universitair Ziekenhuis Gent	Gent	Belgium
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.	Porto	Portugal
Azienda Unita Locale Socio Sanitaria N 8 Berica	Vicenza	Italy
Institut Sainte Catherine	Avignon	France
Unidade Local De Saude De Matosinhos E.P.E.	Senhora Da Hora	Portugal
Unidade Local De Saude Do Alto Ave E.P.E.	Guimaraes	Portugal
Centrul De Oncologie SF Nectarie S.R.L.	Craiova	Romania
Ospedale San Raffaele S.r.l.	Milan	Italy
ASST Grande Ospedale Metropolitano Niguarda	Milan	Italy
Universita’ Degli Studi Di Verona	Verona	Italy
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS	Candiolo	Italy
Catharina Ziekenhuis Stichting	Eindhoven	The Netherlands
IRCCS Ospedale Policlinico San Martino	Genoa	Italy
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca	Cluj Napoca	Romania
St. Luke’s Hospital S.A.	Thessaloniki	Greece
Hopital Beaujon	Clichy	France
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
North Estonia Medical Centre Foundation	Tallin	Estonia
Centre De Lutte Contre Le Cancer Eugene Marquis	Rennes	France
Fundeni Clinical Institute	Bucharest	Romania
Cqrdda Lkxq Bvxxvz	Lyon	France
Hstfquay Ulnktnhbzqdms Mcdjqoc Db Veabxaebyv	Santander	Spain
Izmouudq Cekrnu Dgoynavdjmpnyvmqr	L'hospitalet De Llobregat	Spain
Wrerkwxrgkz Wroqursoscikhgsqulyo Cmbqnkt Odiqwyiaw I Thxqatwylqxkj It Mgmpqximdse W Lleme	Lodz	Poland
Pnhw Tenok Hewsjaek Uosjquclvikr	Sabadell	Spain
Ivsicaqa Rgvyebfdw Pkv Lj Sqlulq Drt Tfyivq Duog Akwgyfd Igwj Seweyr	Meldola	Italy
Sdx Evtrbbtry Hgjxchdj Tgafdef	Tilburg	The Netherlands
Npyxjaam Isiererx Ohispkqgf Isf Mqobg Svntzunwaspgjlsvduvyunxvdrth Iflcgnhw Bygenmhs	Cracow	Poland
Fljwpegrz Pzdy Li Ivtddmzwmbxre Bejwwwnnt Dwj Hjbgzjqj Uqkxtbulzffxb Li Pol	Madrid	Spain
Cbkpop Hxfzqfnbtv E Ukfkjxnkozdzy Dj Cpbbvoj Esooal	Coimbra	Portugal
Halxpctp Vnbu drfpqghk	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	28.10.2021
Estonia	Not recruiting	28.10.2021
France	Not recruiting	28.10.2021
Germany	Not recruiting	28.10.2021
Greece	Not recruiting	28.10.2021
Ireland	Not recruiting	28.10.2021
Italy	Not recruiting	28.10.2021
Poland	Not recruiting	28.10.2021
Portugal	Not recruiting	28.10.2021
Romania	Not recruiting	28.10.2021
Spain	Not recruiting	28.10.2021
The Netherlands	Not recruiting	28.10.2021

Trial locations

Investigated drugs:

Zanidatamab is a medication designed to target HER2-positive cancer cells. It works by attaching to HER2 proteins on cancer cells, which helps stop the cancer from growing and spreading. This medication is being studied for treating advanced gastroesophageal cancer.

Tislelizumab is an immunotherapy medication that helps the body’s immune system fight cancer cells. It works by blocking a protein that normally prevents immune cells from attacking cancer cells, allowing the immune system to better recognize and destroy the cancer.

Trastuzumab is an established cancer medication that also targets HER2-positive cancer cells. It has been used for many years to treat various types of HER2-positive cancers by attaching to the HER2 proteins on cancer cells and helping to slow or stop cancer growth.

Chemotherapy refers to standard cancer-fighting medications that work by killing rapidly dividing cells throughout the body. These medications are commonly used in combination with targeted therapies to treat cancer.

Gastroesophageal Adenocarcinoma (GEA) – A cancer that develops in the cells of the stomach or the junction where the esophagus meets the stomach. The disease begins when healthy cells in the inner lining of these areas become abnormal and grow out of control, forming a tumor. As the cancer progresses, it can grow through the wall of the stomach or esophagus and spread to nearby lymph nodes and other organs. The condition typically develops gradually over time, with cells slowly becoming more abnormal and invasive. GEA can affect the body’s ability to digest food properly and may impact nutrient absorption.

Trial ID:

2023-510319-20-00

Protocol code:

ZWI-ZW25-301

NCT ID:

NCT05152147

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of Zanidatamab and Tislelizumab Combined with Chemotherapy for Patients with Advanced or Metastatic HER2-positive Gastroesophageal Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?