Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300) | NCT02625623

ID	Type	Description	Link
2015-003301-42	EudraCT Number

Name	Class
Merck KGaA, Darmstadt, Germany	INDUSTRY

Label	Type	Description	Intervention Names
Physician choice chemotherapy+Best Supportive Care (BSC)	Experimental	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprises of one of the following: paclitaxel at a dose of 80 milligram per meter square (mg/m^2) on Days 1, 8, and 15 of a 4-week treatment cycle until confirmed progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until confirmed progressive disease or unacceptable toxicity. Participants who are not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above receive BSC alone once every 3 weeks. BSC is defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and is based on investigator's discretion.	Drug: Irinotecan Drug: Paclitaxel Other: Best Supportive Care (BSC)
Avelumab+BSC	Active Comparator	Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with BSC. BSC is defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and is based on investigator's discretion.	Drug: Avelumab Other: Best Supportive Care (BSC)

Name	Type	Description	Arm Group Labels	Other Names
Avelumab	Drug	Avelumab was administered as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with best supportive care (BSC).

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.	From randomization up to 627 days

Measure	Description	Time Frame
Progression Free Survival (PFS)	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). 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subjects aged greater than or equal to (>=) 18 years
Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue
Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry
Adequate hematological, 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 subjects 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
Major surgery
Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to less than [<] 10 mg prednisone daily).
All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, 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 of grade >2 related to prior therapy except neuropathy and alopecia
Neuropathy Grade greater than or equal (>=) 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 subject's tolerance of trial treatment
Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Legal incapacity or limited legal capacity
Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization
Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call

Name	Affiliation	Role
Medical Responsible	Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Rocky Mountain Cancer Centers 1800 Williams Street, Suite 100		Denver	Colorado	80218	United States

PubMed Identifier	Type	Citation	Retractions
30052729	Result	Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. doi: 10.1093/annonc/mdy264.

Label	URL
Trial Awareness and Transparency website	View source

ID	Title	Description
FG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 28, 2018	Nov 20, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival (OS)

OS 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.

FAS included all participants who were randomized to study treatment.

Posted

Median

95% Confidence Interval

months

From randomization up to 627 days

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.
OG001	Avelumab + BSC	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 along with BSC. 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.

Units	Counts
Participants	OG000186 OG001185

Title

Denominators

Categories

Title	Measurements
	OG0005.0(4.5 to 6.3) OG0014.6(3.6 to 5.7)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank	The treatment arms were compared using a stratified, 1-sided, log rank Test. The stratification factor was region (Asia versus non Asia).	0.8078		Hazard Ratio (HR)	1.11			2-Sided	95	0.88	1.41					Superiority

Secondary

Progression Free Survival (PFS)

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). 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.

FAS included all participants who were randomized to study treatment.

Posted

Median

95% Confidence Interval

months

From randomization up to 627 days

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.
OG001

Secondary

Best Overall Response (BOR)

BOR was determined by RECIST v1.1 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 (and not qualifying for CR, PR or SD).

FAS included all participants who were randomized to study treatment.

Posted

Count of Participants

Participants

From randomization up to 627 days

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Secondary

Objective Response Rate (ORR)

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 adjudicated by the Independent Review Committee (IRC). 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.

FAS included all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization up to 627 days

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.
OG001	Avelumab + SC

Secondary

Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)

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.

Health-related quality of life (HRQoL) analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.

Posted

Mean

Standard Deviation

units on a scale

Baseline, EOT (up to Week 66)

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Secondary

Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)

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.

HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.

Posted

Mean

Standard Deviation

millimeter (mm)

Baseline, EOT (up to Week 66)

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Secondary

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)

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.

HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment and had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.

Posted

Mean

Standard Deviation

units on a scale

Baseline, EOT (up to Week 66)

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Secondary

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT)

The 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.

Posted

Mean

Standard Deviation

units on a scale

Baseline, EOT (up to Week 66)

ID	Title	Description
OG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disease progression	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG00030 affected177 at risk EG00139 affected184 at risk
General physical health deterioration	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG00111 affected184 at risk
Asthenia	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0013 affected184 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0016 affected184 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0015 affected184 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0014 affected184 at risk
Ascites	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0013 affected184 at risk
Dysphagia	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0013 affected184 at risk
Ileus	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0004 affected177 at risk EG0012 affected184 at risk
Subileus	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG0011 affected184 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG0010 affected184 at risk
Pneumonia	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0015 affected184 at risk
Sepsis	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0013 affected184 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG0015 affected184 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG0010 affected184 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0004 affected177 at risk EG0012 affected184 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0004 affected177 at risk EG0011 affected184 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG0011 affected184 at risk
Pain	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Pyrexia	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Chills	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Condition aggravated	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Fatigue	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Oedema peripheral	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0010 affected184 at risk
Sudden death	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0012 affected184 at risk
Colitis	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Constipation	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Duodenal obstruction	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Nausea	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0011 affected184 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Gastric stenosis	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Haematemesis	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Haemorrhagic ascites	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Melaena	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Device related infection	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0012 affected184 at risk
Diverticulitis	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Urinary tract infection	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Abdominal infection	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Device related sepsis	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Empyema	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Herpes zoster	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0010 affected184 at risk
Lung infection	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Pulmonary sepsis	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Septic shock	Infections and infestations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Neoplasm swelling	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Pericarditis malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0011 affected184 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Lymphadenopathy mediastinal	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0011 affected184 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Cholangitis	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Dilatation intrahepatic duct acquired	Hepatobiliary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0012 affected184 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG0010 affected184 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0012 affected184 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Alanine aminotransferase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Aspartate aminotransferase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Liver function test increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0011 affected184 at risk
Platelet count decreased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0012 affected184 at risk
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Soft tissue disorder	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Pericardial effusion	Cardiac disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Cardiac arrest	Cardiac disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Tachycardia	Cardiac disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Anastomotic stenosis	Injury, poisoning and procedural complications	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Dizziness	Nervous system disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0012 affected184 at risk
Autoimmune hypothyroidism	Endocrine disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Device occlusion	Product Issues	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0000 affected177 at risk EG0011 affected184 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Renal failure	Renal and urinary disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Deep vein thrombosis	Vascular disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk
Shock symptom	Vascular disorders	MedDRA version 20.0	Non-systematic Assessment	EG0001 affected177 at risk EG0010 affected184 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00061 affected177 at risk EG00134 affected184 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00032 affected177 at risk EG00133 affected184 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00031 affected177 at risk EG00125 affected184 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00054 affected177 at risk EG00124 affected184 at risk
Constipation	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00027 affected177 at risk EG00118 affected184 at risk
Dysphagia	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG0002 affected177 at risk EG00110 affected184 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00018 affected177 at risk EG0017 affected184 at risk
Fatigue	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG00028 affected177 at risk EG00128 affected184 at risk
Asthenia	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG00035 affected177 at risk EG00126 affected184 at risk
Pyrexia	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG00030 affected177 at risk EG00121 affected184 at risk
Chills	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG00119 affected184 at risk
Oedema peripheral	General disorders	MedDRA version 20.0	Non-systematic Assessment	EG00016 affected177 at risk EG0015 affected184 at risk
Aspartate aminotransferase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00013 affected177 at risk EG00116 affected184 at risk
Weight decreased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00012 affected177 at risk EG00116 affected184 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00013 affected177 at risk EG00115 affected184 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00010 affected177 at risk EG00114 affected184 at risk
Alanine aminotransferase increased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00013 affected177 at risk EG00111 affected184 at risk
Neutrophil count decreased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00016 affected177 at risk EG0010 affected184 at risk
White blood cell count decreased	Investigations	MedDRA version 20.0	Non-systematic Assessment	EG00014 affected177 at risk EG0010 affected184 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG00037 affected177 at risk EG00129 affected184 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG00110 affected184 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG00048 affected177 at risk EG00130 affected184 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA version 20.0	Non-systematic Assessment	EG00025 affected177 at risk EG0010 affected184 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 20.0	Non-systematic Assessment	EG0003 affected177 at risk EG00118 affected184 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG0006 affected177 at risk EG00118 affected184 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00010 affected177 at risk EG0018 affected184 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Non-systematic Assessment	EG00015 affected177 at risk EG0017 affected184 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA version 20.0	Non-systematic Assessment	EG00014 affected177 at risk EG0011 affected184 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA version 20.0	Non-systematic Assessment	EG00025 affected177 at risk EG0010 affected184 at risk

ID	Term
D012008	Recurrence
D013274	Stomach Neoplasms

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases

ID	Term
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.
BG001	Avelumab + BSC	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 along with BSC. 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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan 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.	131	177	81	177	150	177
EG001	Avelumab + BSC	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 along with BSC. 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.	142	184	90	184	146	184