Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)

Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction Clinical Trial

Official title:

A Phase III Open-label, Multicenter Trial of Maintenance Therapy With Avelumab (MSB0010718C) Versus Continuation of First-line Chemotherapy in Subjects With Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro-esophageal Junction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02625610
• Other study ID #: EMR 100070-007
• Secondary ID: 2015-003300-23
• Status: Completed
• Phase: Phase 3
• Start date: December 24, 2015
• Est. completion date: June 3, 2021

Study information

• Verified date: May 2022
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to demonstrate superiority of treatment with avelumab versus continuation of first-line chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 499
• Est. completion date: June 3, 2021
• Est. primary completion date: September 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female participants greater than or equal to (>=) 18 years
• Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
• Estimated life expectancy of more than 12 weeks
• Adequate haematological, hepatic and renal functions defined by the protocol
• Negative blood pregnancy test at Screening for women of childbearing potential
• Highly effective contraception for both male and female participants if the risk of conception exists
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
• Concurrent anticancer treatment or immunosuppressive agents
• Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
• Tumor shown to be human epidermal growth factor 2 plus (HER2+)
• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the participant has not fully recovered from the surgery within 4 weeks of enrolment
• Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of participants with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to <= 10 mg prednisone daily)
• All participants with brain metastases, except those meeting the following criteria:

a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)

• Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
• Prior organ transplantation, including allogeneic stem-cell transplantation
• Significant acute or chronic infections
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Persisting toxicity related to prior therapy except alopecia
• Neuropathy Grade > 3
• Pregnancy or lactation
• Known alcohol or drug abuse
• History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
• Clinically significant (i.e., active) cardiovascular disease
• All other significant diseases might impair the participant's tolerance of study treatment
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
• Vaccination with live or live/attenuated viruses within 55 days of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
• Legal incapacity or limited legal capacity
• Participants will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Adenocarcinoma
• Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction

Intervention

Drug:
• Avelumab
Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks.
• Oxaliplatin
Induction Phase: Oxaliplatin was administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
• 5-Fluorouracil
Induction Phase: 5-Fluorouracil was administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
• Leucovorin
Induction Phase: Leucovorin was administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
• Capecitabine
Induction Phase: Capecitabine was administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase every 3 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.

Other:
• Best supportive care
Treatment administered with the intent to maximize Quality of Life (QoL) without a specific antineoplastic regimen. These may include for example antibiotics, analgesics, antiemetics, thoracentesis, paracentesis, blood transfusions, nutritional support (including jejunostomy), and focal external-beam radiation for control of pain, cough, dyspnea, or bleeding. Best supportive care were administered per institutional guidelines and participants were visit the clinic every 3 weeks.

Drug:
• Oxaliplatin
Induction Phase: Oxaliplatin will be administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks.
• 5-Fluorouracil
Induction Phase: 5-Fluorouracil will be administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks.
• Leucovorin
Induction Phase: Leucovorin will be administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.
• Capecitabine
Induction Phase: Capecitabine will be administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.

Locations

Country	Name	City	State
Australia	Ballarat Base Hospital	Ballarat	Victoria
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Monash Medical Centre Clayton	Bentleigh	Victoria
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	St George Hospital	Kogarah	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Border Medical Oncology	Wodonga	Victoria
Brazil	Hospital Infanta Cristina	Badajoz
Brazil	Hospital de Câncer de Barretos-Fundação Pio XII	Barretos	Sao Paulo
Brazil	Hospital São Lucas da PUCRS	Ijuí	Rio Grande Do Sul
Brazil	Hospital Bruno Born	Lajeado	Rio Grande Do Sul
Brazil	Oncosinos - Clínica de Oncologia - Hospital Regina	Novo Hamburgo	Rio Grande Do Sul
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	IMV - Instituto De Medicina Vascular Hospital Mae de Deus	Porto Alegre	Sao Paulo
Brazil	NOB - Núcleo de Oncologia da Bahia	Salvador	Bahia
Brazil	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo Andre	Sao Paulo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	Sao Paulo
Brazil	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo	Sao Paulo
Canada	The Royal Victoria Hospital	Barrie	Ontario
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Cité de la Santé de Laval	Laval	Quebec
Canada	McGill University - Dept. Oncology Clinical Research Program	Montréal	Quebec
Canada	Humber River Hospital	Toronto	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
France	ICO - Site René Gauducheau	Angers Cedex 9	Maine Et Loire
France	CHU Besancon - Hopital Jean Minjoz	Besancon	Doubs
France	CHU Bordeaux	Bordeaux Cedex	Gironde
France	Hôpital Morvan	Brest	Brittany
France	CHU Tours - Hôpital Trousseau	Chambray les Tours	Indre Et Loire
France	CHU Clermont Ferrand	Clermont Ferrand cedex 1	Puy De Dome
France	Centre Georges François Leclerc	Dijon cedex	Côte-d'Or
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans Cedex 02	Sarthe
France	Hôpital de la Timone	Marseille cedex 5	Bouches Du Rhone
France	Centre Antoine Lacassagne	Nice cedex 02	Alpes Maritimes
France	Hôpital Cochin	Paris cedex 14	Paris
France	Hôpital Européen Georges Pompidou	Paris Cedex 15	Paris
France	CRLCC Eugene Marquis	Rennes cedex	Ille Et Vilaine
France	CHU de Toulouse - Hôpital Rangueil	Toulouse Cedex 9	Haute Garonne
Germany	Klinikum Esslingen GmbH	Esslingen A. N.	Baden Wuerttemberg
Germany	Krankenhaus Nordwest GmbH	Frankfurt	Hessen
Germany	Marienkrankenhaus Hamburg	Hamburg
Germany	Onkologische Schwerpunktpraxis Eppendorf	Hamburg
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn	Baden Wuerttemberg
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Rheinland Pfalz
Germany	Klinikum Bogenhausen	Muenchen	Bayern
Germany	Leopoldina Krankenhaus Schweinfurt	Schweinfurt	Bayern
Hungary	Magyar Honvedseg Egeszsegugyi	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen	Hajdú-Bihar
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor	Gyor-Moson-Sopron
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	Pecsi Tudomanyegyetem	Pecs	Baranya
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszard
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
Italy	Presidio Ospedaliero Garibaldi Nesima	Catania
Italy	Azienda Socio Sanitaria Territoriale di Cremona (Istituti Ospitalieri di Cremona)	Cremona
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Seconda Università degli Studi di Napoli	Napoli
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova
Italy	Ospedale degli Infermi	Rimini
Italy	Università Campus Bio-Medico di Roma	Roma
Italy	Azienda Ospedaliera S. Maria Di Terni	Terni
Italy	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia	Udine
Japan	Chiba Cancer Center	Chiba-shi	Chiba-Ken
Japan	Nat Cancer Ctr Hosp	Chuo-ku	Tokyo-To
Japan	Saitama Medical University International Medical Center	Hidaka-shi	Saitama-Ken
Japan	Izumi Municipal Hospital	Izumi-shi	Osaka
Japan	Kagoshima University Medical And Dental Hospital	Kagoshima-shi
Japan	Kagawa University Hospital	Kita-gun	Kagawa-Ken
Japan	Saitama Cancer Center	Kitaadachi-gun	Saitama-Ken
Japan	Kumamoto University Hospital	Kumamoto-shi	Kumamoto-Ken
Japan	Toranomon Hospital	Minato-ku	Tokyo-To
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata-Ken
Japan	Kindai University Hospital	Osakasayama	Osaka-Fu
Japan	Tohoku University Hospital	Sendai-shi	Miyagi-Ken
Japan	Tochigi Cancer Center	Utsunomiya-shi	Tochigi-Ken
Japan	Kanagawa Cancer Center	Yokohama-shi	Kanagawa-Ken
Japan	Oita University Hospital	Yufu-shi	Oita-ken
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu	Jung-gu
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Yonsei University Health System	Seoul
Romania	S.C Oncopremium Team S.R.L	Baia Mare
Romania	Hifu Terramed Conformal SRL	Bucuresti
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Spitalul Clinic Coltea	Bucuresti
Romania	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj Napoca	Cluj
Romania	S.C Radiotherapy Center Cluj S.R.L	Comuna Floresti	Cluj
Romania	S.C Centrul de Oncologie Sf. Nectarie S.R.L	Craiova	Dolj
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Spital Lotus SRL	Ploiesti	Prahova
Romania	S.C Oncocenter Oncologie Clinica S.R.L	Timisoara	Timis
Romania	S.C Oncomed S.R.L	Timisoara	Timis
Russian Federation	SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"	Arkhangelsk
Russian Federation	LLC Evimed	Chelyabinsk
Russian Federation	RBIH "Ivanovo Regional Oncological Dispensary"	Ivanovo
Russian Federation	SBIH " Clinical Oncological Dispensary # 1"	Krasnodar
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	BHI of Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	SBIH of Stavropol territory "Pyatigorsk Oncological Dispensary"	Pyatigorsk
Russian Federation	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	Saint-Petersburg	Leningrado
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint-Petersburg	Leningrado
Russian Federation	SPb SBIH "City Clinical Oncological Dispensary"	Saint-Petersburg
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	ICO l´Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Madrid Sanchinarro	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Muang	Chiang Mai
Thailand	King Chulalongkorn Memorial Hospital	Patumwan	Bangkok
Turkey	Acibadem Adana Hospital	Adana
Turkey	Adana Numune Training and Research Hospital	Adana
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Dicle University, Medical faculty	Diyarbakir
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Marmara University Pendik Research and Training Hospital	Istanbul
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Konya Necmettin Erbakan University Meram Medical Faculty	Konya
Turkey	Inonu Uni. Med. Fac.	Malatya
Turkey	Mersin University Medical Faculty	Mersin
United Kingdom	Ninewells Hospital	Dundee	Tayside Region
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Barts Hospital	London	Greater London
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	The Christie	Manchester	Greater Manchester
United Kingdom	Mount Vernon Hospital	Northwood	Middlesex
United Kingdom	Derriford Hospital	Torquay	Devon
United Kingdom	The Clatterbridge Cancer Centre	Wirral	Merseyside
United States	Comprehensive Blood & Cancer Center	Bakersfield	California
United States	St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	TriHealth Hatton Institute	Cincinnati	Ohio
United States	UC Health Clinical Trials Office	Cincinnati	Ohio
United States	Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Washington - Seattle Cancer Care Alliance	East Seattle	Washington
United States	Virginia Crosson Cancer Center	Fullerton	California
United States	Greenville Hospital System University Medical Center (ITOR)	Greenville	South Carolina
United States	Oncology Consultants, P.A.	Houston	Texas
United States	Franciscan St. Francis Health Cancer Center	Indianapolis	Indiana
United States	Mount Sinai - PRIME	Jamaica	New York
United States	Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	UCLA Medical Center	Los Angeles	California
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Clinical Research Alliance, Inc	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	UF Health Cancer Center Orlando	Orlando	Florida
United States	Oncology Specialists, S.C.	Park Ridge	Illinois
United States	Memorial West Cancer Institute	Pembroke Pines	Florida
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California
United States	University of Rochester	Rochester	New York
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sansum Clinic	Santa Barbara	California
United States	Trio - Central Coast Medical Oncology Corporation	Santa Maria	California
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	University of South Florida - Parent	Tampa	Florida
United States	Baylor Scott & White Health	Temple	Texas
United States	Cotton-O'Neil Clinical Research Center, Hematology and Oncology	Topeka	Kansas
United States	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington
United States	University of Kansas Medical Center Research Institute, Inc.	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Romania,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall Survival was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.	From randomization into maintenance phase up to 1276 days
Secondary	Progression Free Survival (PFS) by Independent Review Committee (IRC)	The PFS time was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurs first). PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as per IRC. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.	From randomization into maintenance phase up to 1276 days
Secondary	Best Overall Response (BOR) by Investigator Assessment	BOR was determined by RECIST v1.1 per Investigator assessment and defined as best-confirmed response of any of following: complete response (CR), partial response (PR), stable disease (SD) and PD recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in SLD of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions. PR or CR confirmed at a subsequent tumor assessment, not sooner than 5 weeks after initial documentation or at an assessment later than the next assessment after the initial documentation of PR or CR. SD confirmed at least 6 weeks after randomization. Confirmed PD equal to progression <=2 weeks after date of randomization.	From randomization into maintenance phase up to 1276 days
Secondary	Objective Response Rate (ORR) by Investigator Assessment	The ORR defined as the percentage of all randomized participants with a confirmed best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1 and as per Investigator assessment. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.	From randomization into maintenance phase up to 1276 days
Secondary	Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score up to Safety Follow-up (Up to 152.3 Weeks)	EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall composite health state index score, with scores ranging from -0.594 to 1. A higher score indicates better health state.	Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Secondary	Change From Baseline in European Quality of Life 5-dimensions Health Outcome Questionnaire Through Visual Analogue Scale up to Safety Follow-up (Up to 152.3 Weeks)	EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.	Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score up to Safety Follow-up (Up to 152.3 Weeks)	European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.	Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22 ) Questionnaire Scores up to Safety Follow-up (Up to 152.3 Weeks)	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22 ) supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.	Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Secondary	Maintenance Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)	Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.	From randomization into maintenance phase up to 1276 days
Secondary	Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values	Blood samples were collected for the analysis of following hematology parameters: lymphocyte count, neutrophil count, white blood cells, platelet count, lipase, serum amylase, creatinine phosphokinase and creatinine. The hematology parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case (Grade 4) post Baseline is presented. Only those participants with increase to grade 4 have been presented.	From baseline up to 1276 days
Secondary	Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Vital signs assessment included Systolic blood pressure (SBP), Diastolic blood pressure (DBP) and Pulse Rate (PR). Number of Participants with any potentially clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.	From randomization into maintenance phase up to 1276 days
Secondary	Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities	ECG parameters included heart rate, pulse rate intervals, QRS interval, QT interval corrected based on Fridericia's formula (QTcF) intervals and QTcB intervals. Clinical significance was determined by the investigator. Number of participants with potentially clinically significant ECG abnormalities were reported.	From randomization into maintenance phase up to 1276 days
Secondary	Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1	ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with shift in ECOG PS Score to 1 or Higher Than 1 were reported.	From randomization into maintenance phase up to 1276 days

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