A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer

Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma Clinical Trial

— Spotlight  

Official title:

A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03504397
• Other study ID #: 8951-CL-0301
• Secondary ID: 2017-002567-17CT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 21, 2018
• Est. completion date: March 31, 2025

Study information

• Verified date: May 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study of zolbetuximab (IMAB362) plus mFOLFOX6 versus placebo plus mFOLFOX6 in subjects with Claudin 18.2 positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Why is this study being done? SPOTLIGHT is a new clinical study for adult patients who have any of: - advanced unresectable gastric or GEJ cancer - metastatic gastric or GEJ cancer. These types of cancers have a unique set of proteins (called Claudin 18.2). We may be able to use a treatment that targets the proteins to kill the cancer cells. For patients with one of the types of cancer listed above, mFOLFOX6 (a combination of three chemotherapies known as Oxaliplatin, Leucovorin, and Fluorouracil) is a current treatment option. This study is testing an experimental medicine called zolbetuximab (IMAB362). Zolbetuximab attaches itself to Claudin 18.2 on the cancer cells causing cancer cell death. Patients will be assigned to one of two groups by chance and given either: - zolbetuximab with mFOLFOX6; or - a placebo with mFOLFOX6. A placebo is a treatment that looks like the experimental medicine, but contains no medicine. The goal of the study is to find out if zolbetuximab with mFOLFOX6 helps patients to live longer by stopping the cancer from getting worse.

Description:

The study consists of the following periods: screening; treatment; post-treatment follow up, safety follow up, long term and survival follow-up. After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 566
• Est. completion date: March 31, 2025
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are

eligible) and at least one of the following conditions applies:

• Not a woman of child-bearing potential (WOCBP) OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
• A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
• Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
• Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
• Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
• Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, = 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy = 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
• Subject's tumor expresses CLDN18.2 in = 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
• Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
• Subject has ECOG performance status 0 to 1.
• Subject has predicted life expectancy = 12 weeks.
• Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
• Hemoglobin (Hgb) = 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb = 9 g/dL.
• Absolute neutrophil count (ANC) = 1.5 x 10^9/L
• Platelets = 100 x 10^9/L
• Albumin = 2.5 g/dL
• Total bilirubin = 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN without liver metastases (or = 5 x ULN if liver metastases are present)
• Estimated creatinine clearance = 30 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion Criteria:

• Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies, as long as it was completed at least 6 months prior to randomization. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization.
• Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma = 14 days prior to randomization and has not recovered from any related toxicity.
• Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
• Subject has received other investigational agents or devices within 28 days prior to randomization.
• Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
• Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
• Subject has known dihydropyrimidine dehydrogenase deficiency.
• Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
• Subject has significant gastric bleeding and/or untreated gastric ulcers that would exclude the subject from participation.
• Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
• For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
• Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
• Subjects treated for HCV with undetectable viral load results are eligible.
• Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
• Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
• Subject has significant cardiovascular disease, including any of the following:
• Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
• History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes)
• QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects
• History or family history of congenital long QT syndrome
• Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
• Subject has a history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
• Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
• Subject has had a major surgical procedure = 28 days prior to randomization.
• Subject is without complete recovery from a major surgical procedure = 14 days prior to randomization.
• Subject has psychiatric illness or social situations that would preclude study compliance.
• Subject has another malignancy for which treatment is required.
• Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer
• Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer
• Metastatic Gastric Adenocarcinoma or Cancer
• Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Intervention

Drug:
• zolbetuximab
Zolbetuximab will be administered as a minimum 2-hour IV infusion.
• placebo
Placebo will be administered as a minimum 2-hour IV infusion.
• oxaliplatin
Oxaliplatin will be administered as a 2-hour IV infusion
• folinic acid
Folinic acid will be administered as a 2-hour IV infusion.
• fluorouracil
Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.

Locations

Country	Name	City	State
Australia	Site AU61008	Adelaide	South Australia
Australia	Site AU61002	Douglas	Queensland
Australia	Site AU61006	East Bentleigh	Victoria
Australia	Site AU61007	Kogarah
Australia	Site AU61011	Tugun	Queensland
Belgium	Site BE32005	Brugge
Belgium	Site BE32004	Brussels
Belgium	Site BE32001	Bruxelles	Bruxelles-Capitale, Région De
Belgium	Site BE32002	Bruxelles	Liege
Belgium	Site BE32011	Charleroi
Belgium	Site BE32007	Edegem	Antwerpen
Belgium	Site BE32012	Gent	Oost-Vlaanderen
Belgium	Site BE32010	Haine-Saint-Paul
Belgium	Site BE32006	Leuven	Vlaams Brabant
Belgium	Site BE32008	Mons	Hainaut
Brazil	Site BR55007	Barretos	São Paulo
Brazil	Site BR55017	Belo Horizonte
Brazil	Site BR55010	Brasília	Distrito Federal
Brazil	Site BR55002	Itajai	Santa Catarina
Brazil	Site BR55006	Lajeado	Rio Grande Do Sul
Brazil	Site BR55016	Passo Fundo
Brazil	Site BR55015	Rio de Janeiro
Brazil	Site BR55018	Santa Catarina
Brazil	Site BR55003	Santo Andre	Sao Paulo
Brazil	Site BR55005	Sao Jose do Rio Preto	Sao Paulo
Brazil	Site BR55004	São Paulo
Brazil	Site BR55009	São Paulo
Canada	Site CA15005	Edmonton	Alberta
Canada	Site CA15002	Montreal	Quebec
Canada	Site CA15008	Montreal	Quebec
Canada	Site CA15009	Saint-John	New Brunswick
Canada	Site CA15011	Toronto	Ontario
Chile	Site CL56003	Providencia	Santiago
Chile	Site CL56008	Providencia
Chile	Site CL56005	Santiago
Chile	Site CL56007	Valdivia
China	Site CN86002	Beijing
China	Site CN86009	Beijing
China	Site CN86003	Haerbin	Heilongjiang
China	Site CN86004	Hangzhou Shi	Zhejiang
China	Site CN86005	Hefei
China	Site CN86006	Nanjing	Jiangsu
China	Site CN86001	Xiamen
China	Site CN86008	Zhengzhou
Colombia	Site CO57009	Bogota	DC
Colombia	Site CO57001	Cali
Colombia	Site CO57005	Cali	Valle
Colombia	Site CO57002	Medellin
Colombia	Site CO57006	Medellín	Antioquia
Colombia	Site CO57007	Monteria	Córdoba
France	Site FR33008	Besancon cedex	Franche-Comte
France	Site FR33010	Brest Cedex	Bretagne
France	Site FR33103	Creteil
France	Site FR33009	Dijon	Bourgogne
France	Site FR33003	Lyon	Rhone
France	Site FR33011	Montpellier Cedex 5	Languedoc-Roussillon
France	Site FR33005	Nice	Provence-Alpes-Côte-d'Azur
France	Site FR33007	Nice Cedex 2
France	Site FR33002	Paris cedex	Paris
France	Site FR33006	Poitiers	Vienne
France	Site FR33001	Rennes	Bretagne
France	Site FR33104	Saint Priest en Jarez
France	Site FR33101	St Herblain	Pays-de-la-Loire
Germany	Site DE49011	Berlin
Germany	Site DE49012	Berlin
Germany	Site DE49010	Dresden	Sachsen
Germany	Site DE49018	Dresden
Germany	Site DE49021	Halle	Sachsen-Anhalt
Germany	Site DE49019	Heilbronn
Germany	Site DE49004	Leipzig	Sachsen
Germany	Site DE49015	Magdeburg	Sachsen-Anhalt
Germany	Site DE49002	Mainz	Rheinland-Pfalz
Germany	Site DE49007	Munchen	Bayern
Germany	Site DE49008	Munich	Bavaria
Israel	Site IL97210	HaDarom
Israel	Site IL97201	Haifa
Israel	Site IL97209	Holon
Israel	Site IL97202	Jerusalem
Israel	Site IL97206	Kfar Saba	HaMerkaz
Israel	Site IL97203	Tel Aviv
Italy	Site IT39013	Ancona
Italy	Site IT39004	Bergamo
Italy	Site IT39009	Cremona
Italy	Site IT39011	Meldola	Forli
Italy	Site IT39006	Milano
Italy	Site IT39008	Milano
Italy	Site IT39021	Modena
Italy	Site IT39020	Monza	Lombardia
Italy	Site IT39016	Padova
Italy	Site IT39012	Parma
Italy	Site IT39018	Perugia
Italy	Site IT39003	Piacenza
Italy	Site IT39019	Pisa
Italy	Site IT39022	Reggio Emilia
Italy	Site IT39015	Roma
Italy	Site IT39026	Terni
Italy	Site IT39024	Turin TO
Italy	Site IT39023	Vicenza	VI
Japan	Site JP81013	Bunkyo-ku	Tokyo
Japan	Site JP81006	Chuo-ku	Tokyo
Japan	Site JP81005	Fukuoka
Japan	Site JP81015	Hidaka	Saitama
Japan	Site JP81003	Kashiwa	Chiba
Japan	Site JP81010	Kitaadachi-gun	Saitama
Japan	Site JP81014	Kobe	Hyogo
Japan	Site JP81008	Koto-ku	Tokyo
Japan	Site JP81002	Matsuyama	Ehime
Japan	Site JP81009	Nagoya	Aichi
Japan	Site JP81004	Osaka
Japan	Site JP81011	Osaka
Japan	Site JP81007	Sapporo	Hokkaido
Japan	Site JP81001	Suita	Osaka
Japan	Site JP81012	Sunto-gun	Shizuoka
Korea, Republic of	Site KR82008	Incheon
Korea, Republic of	Site KR82002	Seongnam-si	Gyeonggi-do
Korea, Republic of	Site KR82003	Seoul
Korea, Republic of	Site KR82004	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Site KR82005	Seoul
Korea, Republic of	Site KR82006	Seoul
Korea, Republic of	Site KR82007	Seoul
Korea, Republic of	Site KR82009	Suwon-si	Gyeonggido [Kyonggi-do]
Mexico	Site MX52001	Aguascalientes
Mexico	Site MX52007	Ciudad de México	Distrito Federal
Mexico	Site MX52003	Distrito Federal
Mexico	Site MX52009	Jalisco
Mexico	Site MX52002	Mexico	Distrito Federal
Mexico	Site MX52004	Oaxaca
Mexico	Site MX52008	San Luis De Potosi
Mexico	Site MX52010	Veracruz, Ver	Veracruz
Peru	Site PE51003	Arequipa
Peru	Site PE51001	Lima
Peru	Site PE51005	Lima
Peru	Site PE51006	Lima
Peru	Site PE51004	San Isidro	Lima
Poland	Site PL48002	Brzozow	Podkarpackie
Poland	Site PL48004	Lublin	Lubuskie
Poland	Site PL48007	Ostroleka	Mazowieckie
Poland	Site PL48009	Warszawa
Poland	Site PL48005	Wieliszew	Mazowieckie
Spain	Site ES34011	Alcorcon	Madrid
Spain	Site ES34010	Avila	Castilla Y Leon
Spain	Site ES34013	Badalona	Barcelona
Spain	Site ES34005	Barcelona
Spain	Site ES34015	Barcelona
Spain	Site ES34016	Barcelona
Spain	Site ES34019	Burgos
Spain	Site ES34004	Madrid
Spain	Site ES34008	Madrid
Spain	Site ES34017	Madrid
Spain	Site ES34003	Murcia
Spain	Site ES34018	Sevilla
Spain	Site ES34006	Zaragoza
Taiwan	Site TW88604	Kaohsiung
Taiwan	Site TW88608	Kaohsiung
Taiwan	Site TW88605	Kwei-Shan	Taoyuan
Taiwan	Site TW88603	Taichung
Taiwan	Site TW88607	Tainan
Taiwan	Site TW88601	Taipei
Taiwan	Site TW88606	Taipei
United Kingdom	Site GB44003	Aberdeen	Aberdeenshire
United Kingdom	Site GB44103	Cambridge
United Kingdom	Site GB44009	Coventry
United Kingdom	Site GB44104	Dundee
United Kingdom	Site GB44008	Leeds
United Kingdom	Site GB44002	London
United Kingdom	Site GB44004	London
United Kingdom	Site GB44101	London	London, City Of
United Kingdom	Site GB44001	Manchester
United Kingdom	Site GB44102	Sutton	Surrey
United States	MultiCare Regional Cancer Center - Gig Harbor	Auburn	Washington
United States	University of Colorado	Aurora	Colorado
United States	CBCC Global Research, Inc. at Comprehensive Blood and Cancer	Bakersfield	California
United States	University of Maryland Medical Center(UMMC)Transplant Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center	Basking Ridge	New Jersey
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Maryland Oncology Hematology	Brandywine	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Memorial Sloan Kettering Cancer Center	Commack	New York
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Nat'l Medical Center	Duarte	California
United States	Inova Dwight and Martha Schar Cancer Institute	Fairfax	Virginia
United States	St. Jude Hospital Yorba Linda	Fullerton	California
United States	Memorial Sloan Kettering Cancer Center	Harrison	New York
United States	Memorial Cancer Institute - West	Hollywood	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Pacific Shores Medical Group	Huntington Beach	California
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Loma Linda University	Loma Linda	California
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	Middletown	Connecticut
United States	Precision Cancer Research -Dayton Physicians Network	Middletown	Ohio
United States	Memorial Sloan Kettering Cancer Center	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Cancer Treatment Centers of America, Atlanta	Newnan	Georgia
United States	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	Orlando Health Inc	Orlando	Florida
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Cancer Treatment Centers of America, Philadelphia	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Arizona	Phoenix	Arizona
United States	Earle A. Chiles Research Institute	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital-Lifespan Cancer Institute	Providence	Rhode Island
United States	University of California Davis	Sacramento	California
United States	Health Partners Institute	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	University of California - San Francisco	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Sanford Cancer Center	Sioux Falls	South Dakota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	The University of Arizona Medical Center	Tucson	Arizona
United States	Memorial Sloan Kettering Cancer Center	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of radiological progressive disease (per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) or death from any cause, whichever is earliest.	Up to 13 months
Secondary	Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death from any cause.	Up to 23 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by Independent Review Committee (IRC) per RECIST 1.1.	Up to 13 months
Secondary	Duration Of Response (DOR)	DOR, defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.	Up to 13 months
Secondary	Safety and tolerability assessed by adverse events (AEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Up to 16 months
Secondary	Number of participants with laboratory assessments abnormalities and or adverse events	Number of participants with potentially clinically significant laboratory values.	Up to 14 months
Secondary	Number of participants with vital signs abnormalities and or adverse events	Number of participants with potentially clinically significant vital sign values.	Up to 14 months
Secondary	Number of participants with electrocardiograms (ECG) abnormalities and or adverse events	Number of participants with potentially clinically significant ECG values.	Up to 14 months
Secondary	Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events	Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.	Up to 13 months
Secondary	Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30) questionnaire	The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.	Up to 16 months
Secondary	HRQoL measured by the QLQ-OG25 questionnaire	The EORTC-QLQ-OG25 instrument evaluates Gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion.	Up to 16 months
Secondary	HRQoL measured by the Global Pain (GP) questionnaire	The GP instrument is a single assessment of overall pain.	Up to 16 months
Secondary	HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire	The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.	Up to 16 months
Secondary	Time to confirmed deterioration (TTCD)	Calculated using the physical function (PF), OG25-Pain and Global Health Status (GHS)/QoL scores as measured by EORTC QLQ-C30 and QLQ-OG25. TTCD is defined as time to first confirmed deterioration (time from randomization to first clinically meaningful deterioration that is confirmed at the next scheduled visit).	Up to 16 months
Secondary	PK of zolbetuximab: Concentration Immediately Prior to Dosing at multiple dosing (Ctrough)	Ctrough will be derived from the PK serum samples collected.	Up to 16 months
Secondary	Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	Up to 16 months