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

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02625610
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 499
• Locations: 200
• Arms: 2
• Actual Duration (Months): 65.3
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction	Drug: Avelumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Capecitabine; Other: Best supportive care; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Capecitabine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 499 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 24, 2015
• Actual Primary Completion Date: Sep 13, 2019
• Actual Study Completion Date: Jun 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy + Best Supportive Care (BSC) In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	Drug: 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.; Drug: 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.; Drug: 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.; Drug: 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.; Drug: 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.; Drug: 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.; Drug: 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.
Experimental: Avelumab In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.	Drug: Avelumab; Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks.; Other Names: MSB0010718C Anti PD-L1

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [From randomization into maintenance phase up to 1276 days]

   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.

Secondary Outcome Measures

1. Progression Free Survival (PFS) by Independent Review Committee (IRC) [From randomization into maintenance phase up to 1276 days]

   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.

2. Best Overall Response (BOR) by Investigator Assessment [From randomization into maintenance phase up to 1276 days]

   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.

3. Objective Response Rate (ORR) by Investigator Assessment [From randomization into maintenance phase up to 1276 days]

   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.

4. 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) [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)]

   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.

5. 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) [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)]

   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.

6. 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) [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)]

   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.

7. 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) [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)]

   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.

8. 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) [From randomization into maintenance phase up to 1276 days]

   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.

9. Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values [From baseline up to 1276 days]

   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.

10. Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs [From randomization into maintenance phase up to 1276 days]

    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.

11. Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities [From randomization into maintenance phase up to 1276 days]

    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.

12. Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1 [From randomization into maintenance phase up to 1276 days]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Blood & Cancer Center	Bakersfield	California	United States	93309
2	Virginia Crosson Cancer Center	Fullerton	California	United States	92835
3	UCLA Medical Center	Los Angeles	California	United States	90095
4	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California	United States	92262
5	Sansum Clinic	Santa Barbara	California	United States	93105
6	Trio - Central Coast Medical Oncology Corporation	Santa Maria	California	United States	93454
7	Norwalk Hospital	Norwalk	Connecticut	United States	6856
8	UF Health Cancer Center Orlando	Orlando	Florida	United States	32806
9	Memorial West Cancer Institute	Pembroke Pines	Florida	United States	33028
10	University of South Florida - Parent	Tampa	Florida	United States	33606
11	Oncology Specialists, S.C.	Park Ridge	Illinois	United States	60068
12	Franciscan St. Francis Health Cancer Center	Indianapolis	Indiana	United States	46237
13	Cedar Rapids Oncology Project	Cedar Rapids	Iowa	United States	52403
14	Cotton-O'Neil Clinical Research Center, Hematology and Oncology	Topeka	Kansas	United States	66604
15	University of Kansas Medical Center Research Institute, Inc.	Westwood	Kansas	United States	66205
16	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
17	Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
18	Mount Sinai - PRIME	Jamaica	New York	United States	11432
19	Clinical Research Alliance, Inc	New York	New York	United States	10021
20	University of Rochester	Rochester	New York	United States	14642
21	UC Health Clinical Trials Office	Cincinnati	Ohio	United States	45206
22	TriHealth Hatton Institute	Cincinnati	Ohio	United States	45220
23	Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center	Columbus	Ohio	United States	43219
24	Oregon Health & Science University	Portland	Oregon	United States	97239
25	St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
26	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
27	Rhode Island Hospital	Providence	Rhode Island	United States	02903
28	Greenville Hospital System University Medical Center (ITOR)	Greenville	South Carolina	United States	29605
29	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-9179
30	Oncology Consultants, P.A.	Houston	Texas	United States	77024
31	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
32	Baylor Scott & White Health	Temple	Texas	United States	76508
33	University of Washington - Seattle Cancer Care Alliance	East Seattle	Washington	United States	98109
34	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
35	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington	United States	98801
36	St George Hospital	Kogarah	New South Wales	Australia	2217
37	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
38	Greenslopes Private Hospital	Greenslopes	Queensland	Australia	4120
39	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4006
40	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
41	Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5112
42	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
43	Ballarat Base Hospital	Ballarat	Victoria	Australia	3350
44	Bendigo Hospital	Bendigo	Victoria	Australia	3550
45	Monash Medical Centre Clayton	Bentleigh	Victoria	Australia	8120
46	Box Hill Hospital	Box Hill	Victoria	Australia	3128
47	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
48	Border Medical Oncology	Wodonga	Victoria	Australia	3690
49	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
50	NOB - Núcleo de Oncologia da Bahia	Salvador	Bahia	Brazil	40170-110
51	Hospital São Lucas da PUCRS	Ijuí	Rio Grande Do Sul	Brazil	98700-000
52	Hospital Bruno Born	Lajeado	Rio Grande Do Sul	Brazil	95900-000
53	Oncosinos - Clínica de Oncologia - Hospital Regina	Novo Hamburgo	Rio Grande Do Sul	Brazil	93510-250
54	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
55	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
56	Hospital de Câncer de Barretos-Fundação Pio XII	Barretos	Sao Paulo	Brazil	14784-400
57	IMV - Instituto De Medicina Vascular Hospital Mae de Deus	Porto Alegre	Sao Paulo	Brazil	90110-270
58	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo Andre	Sao Paulo	Brazil	09060-650
59	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	Sao Paulo	Brazil	15090-000
60	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo	Sao Paulo	Brazil	01246-000
61	Hospital Infanta Cristina	Badajoz		Brazil	06080
62	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
63	The Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
64	Humber River Hospital	Toronto	Ontario	Canada	M3M 0B2
65	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
66	Cité de la Santé de Laval	Laval	Quebec	Canada	H7M 3L9
67	McGill University - Dept. Oncology Clinical Research Program	Montréal	Quebec	Canada	H2W 1S6
68	Centre Antoine Lacassagne	Nice cedex 02	Alpes Maritimes	France	06189
69	Hôpital de la Timone	Marseille cedex 5	Bouches Du Rhone	France	13385
70	Hôpital Morvan	Brest	Brittany	France	29200
71	Centre Georges François Leclerc	Dijon cedex	Côte-d'Or	France	21079
72	CHU Besancon - Hopital Jean Minjoz	Besancon	Doubs	France	25030
73	CHU Bordeaux	Bordeaux Cedex	Gironde	France	33076
74	CHU de Toulouse - Hôpital Rangueil	Toulouse Cedex 9	Haute Garonne	France	31059
75	CRLCC Eugene Marquis	Rennes cedex	Ille Et Vilaine	France	35042
76	CHU Tours - Hôpital Trousseau	Chambray les Tours	Indre Et Loire	France	37170
77	ICO - Site René Gauducheau	Angers Cedex 9	Maine Et Loire	France	49933
78	Hôpital Cochin	Paris cedex 14	Paris	France	75679
79	Hôpital Européen Georges Pompidou	Paris Cedex 15	Paris	France	75015
80	CHU Clermont Ferrand	Clermont Ferrand cedex 1	Puy De Dome	France	63003
81	Clinique Victor Hugo - Centre Jean Bernard	Le Mans Cedex 02	Sarthe	France	72015
82	Klinikum Esslingen GmbH	Esslingen A. N.	Baden Wuerttemberg	Germany	73730
83	SLK-Kliniken Heilbronn GmbH	Heilbronn	Baden Wuerttemberg	Germany	74078
84	Klinikum Bogenhausen	Muenchen	Bayern	Germany	81925
85	Leopoldina Krankenhaus Schweinfurt	Schweinfurt	Bayern	Germany	97422
86	Krankenhaus Nordwest GmbH	Frankfurt	Hessen	Germany	60488
87	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Rheinland Pfalz	Germany	55131
88	Onkologische Schwerpunktpraxis Eppendorf	Hamburg		Germany	20249
89	Marienkrankenhaus Hamburg	Hamburg		Germany	22087
90	Pecsi Tudomanyegyetem	Pecs	Baranya	Hungary	7624
91	Petz Aladar Megyei Oktato Korhaz	Gyor	Győr-Moson-Sopron	Hungary	9024
92	Debreceni Egyetem Klinikai Kozpont	Debrecen	Hajdú-Bihar	Hungary	4032
93	Magyar Honvedseg Egeszsegugyi	Budapest		Hungary	1062
94	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary	4400
95	Tolna Megyei Balassa Janos Korhaz	Szekszard		Hungary	7100
96	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok		Hungary	5000
97	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg		Hungary	8900
98	Presidio Ospedaliero Garibaldi Nesima	Catania		Italy	95100
99	Azienda Socio Sanitaria Territoriale di Cremona (Istituti Ospitalieri di Cremona)	Cremona		Italy	26100
100	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50141
101	Ospedale San Raffaele	Milano		Italy	20132
102	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
103	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
104	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli		Italy	80131
105	Seconda Università degli Studi di Napoli	Napoli		Italy	80131
106	IOV - Istituto Oncologico Veneto IRCCS	Padova		Italy	35128
107	Ospedale degli Infermi	Rimini		Italy	47923
108	Università Campus Bio-Medico di Roma	Roma		Italy	00128
109	Azienda Ospedaliera S. Maria Di Terni	Terni		Italy	5100
110	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia	Udine		Italy	33100
111	Chiba Cancer Center	Chiba-shi	Chiba-Ken	Japan	260-8717
112	Kagawa University Hospital	Kita-gun	Kagawa-Ken	Japan	761-0793
113	Kanagawa Cancer Center	Yokohama-shi	Kanagawa-Ken	Japan	241-8515
114	Kumamoto University Hospital	Kumamoto-shi	Kumamoto-Ken	Japan	860-8556
115	Tohoku University Hospital	Sendai-shi	Miyagi-Ken	Japan	980-8574
116	Niigata Cancer Center Hospital	Niigata-shi	Niigata-Ken	Japan	951-8566
117	Oita University Hospital	Yufu-shi	Oita-ken	Japan	879-5593
118	Kindai University Hospital	Osakasayama	Osaka-Fu	Japan	589-8511
119	Izumi Municipal Hospital	Izumi-shi	Osaka	Japan	594-0071
120	Saitama Medical University International Medical Center	Hidaka-shi	Saitama-Ken	Japan	350-1298
121	Saitama Cancer Center	Kitaadachi-gun	Saitama-Ken	Japan	362-0806
122	Tochigi Cancer Center	Utsunomiya-shi	Tochigi-Ken	Japan	320-0834
123	Nat Cancer Ctr Hosp	Chuo-ku	Tokyo-To	Japan	104-0045
124	Toranomon Hospital	Minato-ku	Tokyo-To	Japan	105-8470
125	Kagoshima University Medical And Dental Hospital	Kagoshima-shi		Japan	890-8520
126	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	28644
127	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
128	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
129	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do	Korea, Republic of	58128
130	Keimyung University Dongsan Hospital	Daegu	Jung-gu	Korea, Republic of	41931
131	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
132	Kyungpook National University Medical Center	Daegu		Korea, Republic of	41404
133	Asan Medical Center	Seoul		Korea, Republic of	05505
134	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
135	Korea University Anam Hospital	Seoul		Korea, Republic of	2841
136	Seoul National University Hospital	Seoul		Korea, Republic of	3080
137	Yonsei University Health System	Seoul		Korea, Republic of	3722
138	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj Napoca	Cluj	Romania	400015
139	S.C Radiotherapy Center Cluj S.R.L	Comuna Floresti	Cluj	Romania	407280
140	S.C Centrul de Oncologie Sf. Nectarie S.R.L	Craiova	Dolj	Romania	200347
141	Spital Lotus SRL	Ploiesti	Prahova	Romania	100011
142	S.C Oncocenter Oncologie Clinica S.R.L	Timisoara	Timis	Romania	300210
143	S.C Oncomed S.R.L	Timisoara	Timis	Romania	300239
144	S.C Oncopremium Team S.R.L	Baia Mare		Romania	430291
145	Institutul Clinic Fundeni	Bucuresti		Romania	022328
146	Spitalul Clinic Coltea	Bucuresti		Romania	030171
147	Hifu Terramed Conformal SRL	Bucuresti		Romania	031864
148	Institutul Regional de Oncologie Iasi	Iasi		Romania	700483
149	Pavlov First Saint Petersburg State Medical University	Saint-Petersburg	Leningrado	Russian Federation	197022
150	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	Saint-Petersburg	Leningrado	Russian Federation	197758
151	SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"	Arkhangelsk		Russian Federation	163045
152	LLC Evimed	Chelyabinsk		Russian Federation	454048
153	RBIH "Ivanovo Regional Oncological Dispensary"	Ivanovo		Russian Federation	153040
154	SBIH " Clinical Oncological Dispensary # 1"	Krasnodar		Russian Federation	350040
155	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow		Russian Federation	115478
156	BHI of Omsk region "Clinical Oncology Dispensary"	Omsk		Russian Federation	644013
157	SBIH of Stavropol territory "Pyatigorsk Oncological Dispensary"	Pyatigorsk		Russian Federation	357502
158	SPb SBIH "City Clinical Oncological Dispensary"	Saint-Petersburg		Russian Federation	197022
159	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
160	ICO l´Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona	Spain	08908
161	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona	Spain	08208
162	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
163	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
164	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	8025
165	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
166	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
167	Hospital Universitario La Paz	Madrid		Spain	28046
168	Hospital Universitario HM Madrid Sanchinarro	Madrid		Spain	28050
169	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
170	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83301
171	China Medical University Hospital	Taichung		Taiwan	40447
172	Taichung Veterans General Hospital	Taichung		Taiwan	40705
173	National Cheng Kung University Hospital	Tainan		Taiwan	704
174	National Taiwan University Hospital	Taipei		Taiwan	10048
175	Mackay Memorial Hospital	Taipei		Taiwan	104
176	Taipei Veterans General Hospital	Taipei		Taiwan	11217
177	Chang Gung Memorial Hospital, Linkou	Taoyuan		Taiwan	33305
178	King Chulalongkorn Memorial Hospital	Patumwan	Bangkok	Thailand	10330
179	Maharaj Nakorn Chiang Mai Hospital	Muang	Chiang Mai	Thailand	50200
180	Siriraj Hospital	Bangkok		Thailand	10700
181	Acibadem Adana Hospital	Adana		Turkey	01130
182	Adana Numune Training and Research Hospital	Adana		Turkey	1240
183	Hacettepe University Medical Faculty	Ankara		Turkey	06100
184	Akdeniz University Medical Faculty	Antalya		Turkey	7058
185	Dicle University, Medical faculty	Diyarbakir		Turkey	21080
186	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
187	Marmara University Pendik Research and Training Hospital	Istanbul		Turkey	34340
188	Kocaeli University Medical Faculty	Kocaeli		Turkey	41380
189	Konya Necmettin Erbakan University Meram Medical Faculty	Konya		Turkey	42100
190	Inonu Uni. Med. Fac.	Malatya		Turkey	44280
191	Mersin University Medical Faculty	Mersin		Turkey	33169
192	Derriford Hospital	Torquay	Devon	United Kingdom	TQ2 7AA
193	Barts Hospital	London	Greater London	United Kingdom	EC1A 7BE
194	University College London Hospitals	London	Greater London	United Kingdom	WC1E 6AG
195	The Christie	Manchester	Greater Manchester	United Kingdom	M20 4BX
196	The Clatterbridge Cancer Centre	Wirral	Merseyside	United Kingdom	CH63 4JY
197	Mount Vernon Hospital	Northwood	Middlesex	United Kingdom	HA6 2RN
198	Royal Surrey County Hospital	Guildford	Surrey	United Kingdom	GU2 7XX
199	Ninewells Hospital	Dundee	Tayside Region	United Kingdom	DD1 9SY
200	St James's University Hospital	Leeds	West Yorkshire	United Kingdom	LS9 7TF

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc. a business of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Jul 17, 2019
• Statistical Analysis Plan - Jul 23, 2019

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02625610
• Other Study ID Numbers: EMR 100070-007; 2015-003300-23
• First Posted: Dec 9, 2015
• Last Update Posted: Jun 9, 2022
• Last Verified: May 1, 2022

• Keywords provided by EMD Serono Research & Development Institute, Inc.: Avelumab; Cancer; Unresectable; Locally advanced; Metastatic; Adenocarcinoma of the stomach; Gastro-esophageal junction
• Additional relevant MeSH terms: Adenocarcinoma; Leucovorin; Fluorouracil; Capecitabine; Oxaliplatin; Avelumab; Levoleucovorin

Study Results

Participant Flow

Pre-assignment Detail	Overall, 1284 participants were screened for this study. Of which 799 participants received at least 1 dose in the Induction Phase, 499 participants were randomized into maintenance phase of the study.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Period Title: Overall Study
STARTED	250	249
Safety-Maintenance Analysis Set	238	243
COMPLETED	250	249
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab	Total
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.	Total of all reporting groups
Overall Participants	250	249	499
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.6 (11.70)	60.7 (11.03)	60.7 (11.36)
Sex: Female, Male (Count of Participants)
Female	83 33.2%	85 34.1%	168 33.7%
Male	167 66.8%	164 65.9%	331 66.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 6%	19 7.6%	34 6.8%
Not Hispanic or Latino	213 85.2%	220 88.4%	433 86.8%
Unknown or Not Reported	22 8.8%	10 4%	32 6.4%
Race/Ethnicity, Customized (Count of Participants)
White	161 64.4%	171 68.7%	332 66.5%
Black or African American	2 0.8%	2 0.8%	4 0.8%
Asian	59 23.6%	61 24.5%	120 24%
American Indian or Alaska Native	2 0.8%	0 0%	2 0.4%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%
Not collected at this site	22 8.8%	12 4.8%	34 6.8%
Other	3 1.2%	3 1.2%	6 1.2%
Missing	1 0.4%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants included in treatment arm to which they were randomized.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	250	249
Median (95% Confidence Interval) [months]	10.9	10.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemotherapy + Best Supportive Care (BSC), Avelumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1779
	Comments
	Method	Log Rank
	Comments	The treatment arms were compared using a stratified, 1-sided, log rank Test. The stratification factor was region (Asia versus non Asia).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS) by Independent Review Committee (IRC)
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants included in treatment arm to which they were randomized.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	250	249
Median (95% Confidence Interval) [months]	4.4	3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemotherapy + Best Supportive Care (BSC), Avelumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Best Overall Response (BOR) by Investigator Assessment
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants included in treatment arm to which they were randomized.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	250	249
Complete response	5 2%	8 3.2%
Partial response	31 12.4%	25 10%
Stable disease	117 46.8%	92 36.9%
Noncomplete response/non progressive disease	11 4.4%	10 4%
Progressive disease	58 23.2%	85 34.1%
Non evaluable	28 11.2%	29 11.6%

4. Secondary Outcome

Title	Objective Response Rate (ORR) by Investigator Assessment
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants included in treatment arm to which they were randomized.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	250	249
Number (95% Confidence Interval) [percentage of participants]	14.4 5.8%	13.3 5.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemotherapy + Best Supportive Care (BSC), Avelumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set included randomized participants who had 1 Maintenance Phase Baseline HRQoL assessment and had at least 1 post-Maintenance Phase Baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	159	186
Week 3/4	-0.002 (0.1242)	0.004 (0.1610)
Week 7	-0.032 (0.1644)	-0.009 (0.1588)
Week 13	-0.053 (0.1733)	-0.017 (0.1599)
Week 19	-0.039 (0.1934)	-0.011 (0.1556)
Week 25	-0.049 (0.1797)	0.014 (0.1518)
Week 31	-0.023 (0.1619)	0.013 (0.1665)
Week 37	-0.035 (0.1505)	0.013 (0.2234)
Week 43	-0.046 (0.1360)	0.058 (0.1990)
Week 49	-0.100 (0.1796)	0.026 (0.1936)
Week 55	-0.164 (0.2056)	0.028 (0.2067)
Week 61	-0.091 (0.2229)	0.031 (0.1364)
Week 67	-0.076 (0.2347)	0.039 (0.1954)
End Of Treatment	-0.125 (0.2432)	-0.138 (0.2461)
Safety Follow-Up	-0.062 (0.2391)	-0.099 (0.1942)

6. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set included randomized participants who had 1 Maintenance Phase Baseline HRQoL assessment and had at least 1 post-Maintenance Phase Baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	159	186
Week 3/4	0.9 (13.94)	0.6 (13.11)
Week 7	-0.5 (13.59)	-2.1 (14.09)
Week 13	-3.2 (12.83)	-0.7 (13.41)
Week 19	-3.5 (16.39)	-0.1 (14.93)
Week 25	-4.5 (15.66)	-1.4 (15.76)
Week 31	-2.3 (13.14)	1.4 (17.61)
Week 37	-1.7 (11.78)	0.9 (20.39)
Week 43	-4.4 (11.92)	3.2 (15.34)
Week 49	-2.9 (8.95)	2.1 (13.04)
Week 55	-9.4 (16.32)	3.4 (16.52)
Week 61	-6.4 (18.09)	3.5 (16.15)
Week 67	-7.3 (17.10)	4.9 (17.31)
End Of Treatment	-12.2 (22.39)	-10.3 (20.84)
Safety Follow-Up	-8.0 (19.24)	-9.6 (20.30)

7. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set included randomized participants who had 1 Maintenance Phase Baseline HRQoL assessment and had at least 1 post-Maintenance Phase Baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	160	186
Week 3/4	1.30 (15.486)	0.85 (15.021)
Week 7	-1.44 (14.905)	-1.01 (16.967)
Week 13	-2.50 (15.424)	0.24 (17.637)
Week 19	-5.85 (18.363)	1.37 (18.611)
Week 25	-4.43 (15.407)	0.41 (16.204)
Week 31	-3.09 (19.902)	1.85 (16.938)
Week 37	-1.39 (22.186)	1.77 (19.293)
Week 43	-1.19 (12.167)	3.33 (18.518)
Week 49	1.52 (9.731)	4.01 (15.907)
Week 55	0.00 (11.785)	4.00 (15.426)
Week 61	-5.00 (13.944)	2.38 (15.622)
Week 67	0.00 (9.129)	4.90 (18.413)
End Of Treatment	-11.54 (23.460)	-11.67 (21.409)
Safety Follow-Up	-7.51 (19.475)	-9.29 (24.881)

8. Secondary Outcome

Title	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)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set included randomized participants who had 1 Maintenance Phase Baseline HRQoL assessment and had at least 1 post-Maintenance Phase Baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	160	186
Dysphagia: Week 3/4	0.76 (13.371)	0.60 (15.227)
Dysphagia Week 7	2.84 (15.258)	1.34 (13.453)
Dysphagia Week 13	1.60 (14.090)	0.65 (12.781)
Dysphagia Week 19	-0.58 (15.772)	1.52 (14.307)
Dysphagia Week 25	-1.39 (10.465)	1.69 (14.852)
Dysphagia Week 31	0.82 (14.755)	4.39 (20.877)
Dysphagia Week 37	-7.19 (17.977)	-0.67 (14.683)
Dysphagia Week 43	-4.76 (14.265)	-2.59 (13.270)
Dysphagia Week 49	-3.03 (8.736)	1.23 (13.195)
Dysphagia Week 55	0.00 (13.608)	0.89 (13.194)
Dysphagia Week 61	0.00 (15.713)	1.06 (12.123)
Dysphagia Week 67	-1.85 (10.924)	1.31 (17.516)
Dysphagia End Of Treatment	7.27 (25.134)	8.21 (22.633)
Dysphagia Safety Follow-Up	9.39 (21.467)	7.25 (19.417)
Pain Week 3/4	1.51 (13.013)	-0.04 (13.465)
Pain Week 7	2.53 (15.351)	2.60 (15.210)
Pain Week 13	2.96 (14.585)	0.16 (13.523)
Pain Week 19	3.22 (14.152)	-0.51 (14.088)
Pain Week 25	-1.56 (13.789)	-1.55 (17.540)
Pain Week 31	4.01 (19.111)	0.97 (18.564)
Pain Week 37	-4.90 (19.777)	-1.26 (12.346)
Pain Week 43	1.79 (18.251)	-1.94 (14.129)
Pain Week 49	1.52 (5.025)	-0.62 (12.853)
Pain Week 55	0.00 (19.543)	-1.00 (10.012)
Pain Week 61	3.33 (9.501)	-1.59 (13.596)
Pain Week 67	0.00 (12.910)	-0.49 (15.721)
Pain End Of Treatment	9.25 (20.853)	9.45 (22.960)
Pain Safety Follow-Up	8.22 (18.011)	10.99 (20.931)
Reflux Week 3/4	1.04 (14.197)	0.12 (13.571)
Reflux Week 7	0.31 (14.695)	0.50 (17.807)
Reflux Week 13	0.99 (14.098)	-1.09 (15.753)
Reflux Week 19	1.75 (17.032)	-1.68 (15.377)
Reflux Week 25	0.69 (14.648)	1.69 (19.770)
Reflux Week 31	-2.06 (14.791)	-1.29 (18.339)
Reflux Week 37	-6.54 (18.864)	-4.38 (17.773)
Reflux Week 43	-3.17 (15.364)	-5.56 (16.699)
Reflux Week 49	1.01 (9.236)	-2.06 (16.317)
Reflux Week 55	2.22 (4.969)	-3.56 (19.699)
Reflux Week 61	6.67 (9.938)	-6.35 (12.944)
Reflux Week 67	7.41 (13.456)	0.00 (19.245)
Reflux End of Treatment	3.43 (19.529)	4.73 (20.455)
Reflux Safety Follow-up	1.56 (20.254)	2.90 (19.212)
Eating Restrictions Week 3/4	0.73 (16.279)	0.13 (15.438)
Eating Restrictions Week 7	0.98 (16.123)	-0.27 (15.516)
Eating Restrictions Week 13	1.02 (14.234)	0.00 (14.023)
Eating Restrictions Week 19	-2.34 (16.648)	-0.63 (11.993)
Eating Restrictions Week 25	-2.08 (18.208)	-1.55 (15.434)
Eating Restrictions Week 31	-2.47 (15.814)	0.39 (14.880)
Eating Restrictions Week 37	-8.82 (21.943)	-3.28 (15.014)
Eating Restrictions Week 43	-4.76 (18.115)	-3.89 (13.443)
Eating Restrictions Week 49	0.76 (11.459)	-5.25 (12.043)
Eating Restrictions Week 55	3.33 (15.138)	-6.00 (12.620)
Eating Restrictions Week 61	0.00 (15.590)	-5.56 (12.999)
Eating Restrictions Week 67	1.39 (13.351)	-2.45 (19.712)
Eating Restrictions EOT	8.27 (20.898)	10.01 (22.055)
Eating Restrictions Safety Follow-up	7.04 (24.055)	11.59 (25.050)
Anxiety Week 3/4	-0.28 (16.150)	-4.06 (18.030)
Anxiety Week 7	-1.30 (16.947)	-1.20 (20.580)
Anxiety Week 13	-0.86 (20.685)	-2.83 (16.300)
Anxiety Week 19	-1.56 (21.561)	-1.68 (19.220)
Anxiety Week 25	-2.78 (23.780)	-1.69 (14.562)
Anxiety Week 31	4.12 (23.700)	-0.52 (24.119)
Anxiety Week 37	-3.92 (20.765)	-1.01 (27.409)
Anxiety Week 43	-3.97 (22.480)	-1.11 (24.474)
Anxiety Week 49	0.00 (12.172)	-6.17 (17.792)
Anxiety Week 55	2.22 (9.296)	-4.00 (20.000)
Anxiety Week 61	-4.44 (12.669)	-4.76 (24.488)
Anxiety Week 67	9.26 (16.355)	-1.96 (24.918)
Anxiety End of Treatment	4.58 (21.868)	5.89 (23.939)
Anxiety Safety Follow-Up	5.48 (24.116)	4.99 (26.234)

9. Secondary Outcome

Title	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)
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Safety-Maintenance Analysis Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	238	243
Any TEAEs	214 85.6%	223 89.6%
Any Serious TEAE	75 30%	89 35.7%

10. Secondary Outcome

Title	Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values
Description	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.
Time Frame	From baseline up to 1276 days

Outcome Measure Data

Analysis Population Description

Safety-Maintenance Analysis (SMA) Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	238	243
lymphocyte count decreased	0 0%	1 0.4%
neutrophil count decreased	6 2.4%	1 0.4%
white blood cells decreased	2 0.8%	0 0%
platelet count decreased	1 0.4%	0 0%
lipase increased	6 2.4%	8 3.2%
serum amylase increased	3 1.2%	2 0.8%
creatinine phosphokinase increased	0 0%	2 0.8%
creatinine increased	0 0%	1 0.4%

11. Secondary Outcome

Title	Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Safety-Maintenance Analysis Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	238	243
Increased in Systolic blood pressure	57 22.8%	62 24.9%
Decreased in Systolic blood pressure	43 17.2%	69 27.7%
Increased in Diastolic blood pressure	14 5.6%	24 9.6%
Decreased in Diastolic blood pressure	21 8.4%	26 10.4%
Increased in pulse rate	46 18.4%	48 19.3%
Decreased in pulse rate	32 12.8%	30 12%

12. Secondary Outcome

Title	Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Safety-Maintenance Analysis Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	238	243
Decreased heart rate	0 0%	1 0.4%
Increased heart rate	2 0.8%	2 0.8%
Increased Pulse Rate interval	1 0.4%	3 1.2%
Increased QRS interval	5 2%	8 3.2%
QTcF interval greater than (>)450milisecond (ms)less than or equal to(<=)480ms	9 3.6%	9 3.6%
QTcF interval: > 480 ms <= 500 ms	2 0.8%	3 1.2%
QTcF interval: > 500 ms	3 1.2%	1 0.4%
QTcB Interval: > 450 msec <= 480 msec	19 7.6%	18 7.2%
QTcB Interval: > 480 msec <= 500 msec	2 0.8%	2 0.8%
QTcB Interval: > 500 msec	5 2%	3 1.2%

13. Secondary Outcome

Title	Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1
Description	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.
Time Frame	From randomization into maintenance phase up to 1276 days

Outcome Measure Data

Analysis Population Description

Safety-Maintenance Analysis Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.

Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)	Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
Measure Participants	238	243
Count of Participants [Participants]	140 56%	144 57.8%

Adverse Events

Time Frame	From randomization into maintenance phase up to 1276 days
Adverse Event Reporting Description	Safety-Maintenance Analysis Set included all participants who were administered any dose of the maintenance phase study medication or participants randomized to the chemotherapy arm who are designated to receive BSC only. Participants included in the treatment arm according to study treatment actually received.
Arm/Group Title	Chemotherapy + Best Supportive Care (BSC)		Avelumab
Arm/Group Description	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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/Leucovorin (LV) or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.		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 at a dose of 200 mg/m^2 or 400 mg/m^2 on Day 1 followed by 5-Fluorouracil at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 or at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Day 1 and 2) every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks for up to 12 weeks in Induction phase. In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
All Cause Mortality
	Chemotherapy + Best Supportive Care (BSC)		Avelumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/238 (5.5%)		16/243 (6.6%)
Serious Adverse Events
	Chemotherapy + Best Supportive Care (BSC)		Avelumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/238 (31.5%)		89/243 (36.6%)
Blood and lymphatic system disorders
Anaemia	3/238 (1.3%)		2/243 (0.8%)
Neutropenia	3/238 (1.3%)		1/243 (0.4%)
Febrile neutropenia	1/238 (0.4%)		0/243 (0%)
Haemolytic anaemia	1/238 (0.4%)		0/243 (0%)
Thrombotic microangiopathy	1/238 (0.4%)		0/243 (0%)
Cardiac disorders
Myocardial infarction	0/238 (0%)		1/243 (0.4%)
Myocarditis	0/238 (0%)		1/243 (0.4%)
Pericarditis	0/238 (0%)		1/243 (0.4%)
Prinzmetal angina	0/238 (0%)		1/243 (0.4%)
Acute coronary syndrome	1/238 (0.4%)		0/243 (0%)
Acute myocardial infarction	1/238 (0.4%)		0/243 (0%)
Atrioventricular block complete	1/238 (0.4%)		0/243 (0%)
Coronary artery disease	1/238 (0.4%)		0/243 (0%)
Pericardial effusion	2/238 (0.8%)		0/243 (0%)
Endocrine disorders
Adrenal insufficiency	0/238 (0%)		1/243 (0.4%)
Hyperthyroidism	0/238 (0%)		1/243 (0.4%)
Hypophysitis	0/238 (0%)		1/243 (0.4%)
Eye disorders
Diplopia	0/238 (0%)		1/243 (0.4%)
Cataract	1/238 (0.4%)		0/243 (0%)
Gastrointestinal disorders
Dysphagia	2/238 (0.8%)		6/243 (2.5%)
Abdominal pain	2/238 (0.8%)		4/243 (1.6%)
Vomiting	4/238 (1.7%)		4/243 (1.6%)
Ascites	3/238 (1.3%)		3/243 (1.2%)
Colitis	0/238 (0%)		3/243 (1.2%)
Ileus	0/238 (0%)		3/243 (1.2%)
Obstruction gastric	4/238 (1.7%)		3/243 (1.2%)
Diarrhoea	0/238 (0%)		2/243 (0.8%)
Intestinal obstruction	0/238 (0%)		2/243 (0.8%)
Constipation	1/238 (0.4%)		1/243 (0.4%)
Gastric stenosis	2/238 (0.8%)		1/243 (0.4%)
Gastrointestinal haemorrhage	1/238 (0.4%)		1/243 (0.4%)
Large intestine perforation	0/238 (0%)		1/243 (0.4%)
Oesophageal stenosis	0/238 (0%)		1/243 (0.4%)
Pancreatitis	0/238 (0%)		1/243 (0.4%)
Pancreatitis acute	0/238 (0%)		1/243 (0.4%)
Small intestinal obstruction	0/238 (0%)		1/243 (0.4%)
Subileus	1/238 (0.4%)		1/243 (0.4%)
Upper gastrointestinal haemorrhage	2/238 (0.8%)		1/243 (0.4%)
Abdominal hernia	1/238 (0.4%)		0/243 (0%)
Abdominal pain upper	1/238 (0.4%)		0/243 (0%)
Dyspepsia	1/238 (0.4%)		0/243 (0%)
Gastritis	0/238 (0%)		1/243 (0.4%)
Gastric haemorrhage	4/238 (1.7%)		0/243 (0%)
Gastric ulcer	1/238 (0.4%)		0/243 (0%)
Intestinal ischaemia	1/238 (0.4%)		0/243 (0%)
Large intestinal obstruction	1/238 (0.4%)		0/243 (0%)
Melaena	1/238 (0.4%)		0/243 (0%)
Nausea	2/238 (0.8%)		0/243 (0%)
General disorders
Disease progression	6/238 (2.5%)		14/243 (5.8%)
Pyrexia	2/238 (0.8%)		4/243 (1.6%)
Asthenia	0/238 (0%)		1/243 (0.4%)
General physical health deterioration	1/238 (0.4%)		1/243 (0.4%)
Malaise	0/238 (0%)		1/243 (0.4%)
Hepatobiliary disorders
Jaundice cholestatic	1/238 (0.4%)		2/243 (0.8%)
Bile duct obstruction	1/238 (0.4%)		1/243 (0.4%)
Bile duct stenosis	0/238 (0%)		1/243 (0.4%)
Cholecystitis acute	0/238 (0%)		1/243 (0.4%)
Hepatic failure	1/238 (0.4%)		1/243 (0.4%)
Cholangitis	1/238 (0.4%)		0/243 (0%)
Hepatitis	1/238 (0.4%)		0/243 (0%)
Jaundice	1/238 (0.4%)		0/243 (0%)
Immune system disorders
Contrast media reaction	0/238 (0%)		1/243 (0.4%)
Drug hypersensitivity	3/238 (1.3%)		1/243 (0.4%)
Infections and infestations
Device related infection	0/238 (0%)		2/243 (0.8%)
Pneumonia	2/238 (0.8%)		2/243 (0.8%)
Urinary tract infection	2/238 (0.8%)		2/243 (0.8%)
Influenza	1/238 (0.4%)		1/243 (0.4%)
Lower respiratory tract infection	1/238 (0.4%)		1/243 (0.4%)
Lung infection	0/238 (0%)		1/243 (0.4%)
Respiratory tract infection	0/238 (0%)		1/243 (0.4%)
Enteritis infectious	1/238 (0.4%)		0/243 (0%)
Sepsis	1/238 (0.4%)		0/243 (0%)
Septic shock	1/238 (0.4%)		0/243 (0%)
Wound infection	1/238 (0.4%)		0/243 (0%)
Injury, poisoning and procedural complications
Anastomotic stenosis	0/238 (0%)		1/243 (0.4%)
Anastomotic ulcer haemorrhage	0/238 (0%)		1/243 (0.4%)
Overdose	1/238 (0.4%)		1/243 (0.4%)
Chemical burn of respiratory tract	1/238 (0.4%)		0/243 (0%)
Gastrointestinal stoma complication	1/238 (0.4%)		0/243 (0%)
Gastrostomy tube site complication	1/238 (0.4%)		0/243 (0%)
Infusion related reaction	3/238 (1.3%)		0/243 (0%)
Limb injury	1/238 (0.4%)		0/243 (0%)
Investigations
Blood bilirubin increased	0/238 (0%)		1/243 (0.4%)
Lipase increased	1/238 (0.4%)		0/243 (0%)
Metabolism and nutrition disorders
Decreased appetite	4/238 (1.7%)		4/243 (1.6%)
Dehydration	1/238 (0.4%)		1/243 (0.4%)
Failure to thrive	0/238 (0%)		1/243 (0.4%)
Hypokalaemia	1/238 (0.4%)		0/243 (0%)
Hyponatraemia	2/238 (0.8%)		0/243 (0%)
Hypophagia	1/238 (0.4%)		0/243 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/238 (0%)		2/243 (0.8%)
Back pain	1/238 (0.4%)		2/243 (0.8%)
Groin pain	0/238 (0%)		1/243 (0.4%)
Myositis	0/238 (0%)		1/243 (0.4%)
Musculoskeletal pain	1/238 (0.4%)		0/243 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges	1/238 (0.4%)		2/243 (0.8%)
Malignant ascites	0/238 (0%)		1/243 (0.4%)
Tumour haemorrhage	0/238 (0%)		1/243 (0.4%)
Metastases to liver	1/238 (0.4%)		0/243 (0%)
Oesophageal carcinoma recurrent	0/238 (0%)		1/243 (0.4%)
Nervous system disorders
Headache	0/238 (0%)		1/243 (0.4%)
Seizure	0/238 (0%)		1/243 (0.4%)
Cerebral infarction	2/238 (0.8%)		0/243 (0%)
Cerebrovascular accident	1/238 (0.4%)		0/243 (0%)
Dizziness	1/238 (0.4%)		0/243 (0%)
Haemorrhage intracranial	1/238 (0.4%)		0/243 (0%)
Product Issues
Device occlusion	1/238 (0.4%)		0/243 (0%)
Renal and urinary disorders
Hydronephrosis	1/238 (0.4%)		1/243 (0.4%)
Tubulointerstitial nephritis	0/238 (0%)		1/243 (0.4%)
Haematuria	1/238 (0.4%)		0/243 (0%)
Renal tubular necrosis	1/238 (0.4%)		0/243 (0%)
Urinary tract obstruction	1/238 (0.4%)		0/243 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/238 (0.4%)		4/243 (1.6%)
Asphyxia	0/238 (0%)		2/243 (0.8%)
Dyspnoea	1/238 (0.4%)		2/243 (0.8%)
Pneumonia aspiration	0/238 (0%)		1/243 (0.4%)
Pulmonary embolism	1/238 (0.4%)		1/243 (0.4%)
Acute respiratory failure	1/238 (0.4%)		0/243 (0%)
Lung disorder	1/238 (0.4%)		0/243 (0%)
Pleural effusion	3/238 (1.3%)		0/243 (0%)
Respiratory failure	1/238 (0.4%)		0/243 (0%)
Surgical and medical procedures
Nephrostomy	0/238 (0%)		1/243 (0.4%)
Vascular disorders
Embolism	1/238 (0.4%)		2/243 (0.8%)
Deep vein thrombosis	0/238 (0%)		1/243 (0.4%)
Hypotension	1/238 (0.4%)		0/243 (0%)
Other (Not Including Serious) Adverse Events
	Chemotherapy + Best Supportive Care (BSC)		Avelumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	203/238 (85.3%)		191/243 (78.6%)
Blood and lymphatic system disorders
Anaemia	48/238 (20.2%)		35/243 (14.4%)
Neutropenia	36/238 (15.1%)		12/243 (4.9%)
Leukopenia	17/238 (7.1%)		9/243 (3.7%)
Thrombocytopenia	34/238 (14.3%)		8/243 (3.3%)
Gastrointestinal disorders
Nausea	52/238 (21.8%)		41/243 (16.9%)
Abdominal Pain	24/238 (10.1%)		34/243 (14%)
Vomiting	27/238 (11.3%)		30/243 (12.3%)
Constipation	18/238 (7.6%)		28/243 (11.5%)
Diarrhoea	39/238 (16.4%)		27/243 (11.1%)
Abdominal pain upper	5/238 (2.1%)		22/243 (9.1%)
Dyspepsia	15/238 (6.3%)		11/243 (4.5%)
General disorders
Fatigue	29/238 (12.2%)		35/243 (14.4%)
Asthenia	24/238 (10.1%)		30/243 (12.3%)
Pyrexia	28/238 (11.8%)		28/243 (11.5%)
Chills	4/238 (1.7%)		19/243 (7.8%)
Infections and infestations
Upper respiratory tract infection	12/238 (5%)		11/243 (4.5%)
Injury, poisoning and procedural complications
Infusion related reaction	7/238 (2.9%)		18/243 (7.4%)
Investigations
Blood creatine phosphokinase increased	6/238 (2.5%)		19/243 (7.8%)
Gamma-glutamyltransferase increased	15/238 (6.3%)		18/243 (7.4%)
Aspartate aminotransferase increased	17/238 (7.1%)		17/243 (7%)
Blood alkaline phosphatase increased	16/238 (6.7%)		17/243 (7%)
Blood cholesterol increased	10/238 (4.2%)		15/243 (6.2%)
Lipase increased	22/238 (9.2%)		15/243 (6.2%)
Amylase increased	13/238 (5.5%)		14/243 (5.8%)
Alanine aminotransferase increased	12/238 (5%)		13/243 (5.3%)
Weight decreased	19/238 (8%)		12/243 (4.9%)
Blood bilirubin increased	13/238 (5.5%)		9/243 (3.7%)
Platelet count decreased	34/238 (14.3%)		6/243 (2.5%)
Neutrophil count decreased	35/238 (14.7%)		4/243 (1.6%)
Metabolism and nutrition disorders
Decreased appetite	42/238 (17.6%)		26/243 (10.7%)
Hyperglycaemia	9/238 (3.8%)		14/243 (5.8%)
Musculoskeletal and connective tissue disorders
Back Pain	7/238 (2.9%)		17/243 (7%)
Arthralgia	4/238 (1.7%)		16/243 (6.6%)
Nervous system disorders
Headache	6/238 (2.5%)		17/243 (7%)
Peripheral sensory neuropathy	42/238 (17.6%)		14/243 (5.8%)
Dizziness	8/238 (3.4%)		13/243 (5.3%)
Paraesthesia	22/238 (9.2%)		11/243 (4.5%)
Neuropathy peripheral	32/238 (13.4%)		7/243 (2.9%)
Psychiatric disorders
Insomnia	9/238 (3.8%)		16/243 (6.6%)
Skin and subcutaneous tissue disorders
Pruritus	2/238 (0.8%)		17/243 (7%)
Rash	5/238 (2.1%)		15/243 (6.2%)
Palmar-plantar erythrodysaesthesia syndrome	19/238 (8%)		1/243 (0.4%)
Vascular disorders
Hypertension	6/238 (2.5%)		14/243 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.