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

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02625623
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 371
• Locations: 75
• Arms: 2
• Actual Duration (Months): 46.5
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to demonstrate superiority of treatment with avelumab plus best supportive care (BSC) versus physician's choice (chosen from a pre-specified list of therapeutic options) plus BSC.

Condition or Disease	Intervention/Treatment	Phase
Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma; Gastric Cancer Third Line	Drug: Avelumab; Drug: Irinotecan; Drug: Paclitaxel; Other: Best Supportive Care (BSC)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 371 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-label, Multicenter Trial of Avelumab (MSB0010718C) as a Third-line Treatment of Unresectable, Recurrent, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
• Actual Study Start Date: Dec 28, 2015
• Actual Primary Completion Date: Sep 14, 2017
• Actual Study Completion Date: Nov 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Physician choice chemotherapy+Best Supportive Care (BSC) 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; Irinotecan was administered at a dose of 150 mg/m ^2 on Day 1 and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.; Drug: Paclitaxel; Paclitaxel was administered at a dose of 80 mg/m^2 on Day 1, 8, and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.; Other: Best Supportive Care (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. BSC was administered once every 3 weeks.
Active Comparator: Avelumab+BSC 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; 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).; Other Names: MSB0010718C Anti PD-L1 ; Other: Best Supportive Care (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. BSC was administered once every 3 weeks.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [From randomization up to 627 days]

   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.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [From randomization up to 627 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). 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) [From randomization up to 627 days]

   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).

3. Objective Response Rate (ORR) [From randomization up to 627 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 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.

4. 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) [Baseline, EOT (up to Week 66)]

   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 (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) [Baseline, EOT (up to Week 66)]

   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 at End of Treatment (EOT) [Baseline, EOT (up to Week 66)]

   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 at End of Treatment (EOT) [Baseline, EOT (up to Week 66)]

   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.

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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Centers 1800 Williams Street, Suite 100	Denver	Colorado	United States	80218
2	Rocky Mountain Cancer Centers, LLP 3676 Parker Blvd #350	Pueblo	Colorado	United States	81008
3	Advanced Medical Specialties 8940 North Kendall Drive, Suite 300E	Miami	Florida	United States	33176
4	Ocala Oncology Center, P.L. 433 S.W. 10th Street	Ocala	Florida	United States	34471
5	Florida Cancer Specialists 560 Jackson Street, Suite 220	Saint Petersburg	Florida	United States	33705
6	Ingalls Memorial Hospital One Ingalls Drive, W741	Harvey	Illinois	United States	60426
7	Illinois Cancer Specialists 8915 W. Golf Rd.	Niles	Illinois	United States	60714
8	Oncology Specialists, S.C. 1700 Luther Ln, Ste 2200, Park Ridge, IL 60068 7900 Milwaukee Ave, Ste 16	Niles	Illinois	United States	60714
9	Carle Cancer Center 509 W. University Avenue	Urbana	Illinois	United States	61801
10	Cotton-O'Neil Clinical Research Center, Hematology and Oncology and Stormont Vail Cancer Center 1414 SW 8th St	Topeka	Kansas	United States	66604
11	Metairie Oncologist, LLC Office of Jayne Gurtler MD, Laura Brinz MD, Janet Burroff MD 3939 Houma Blvd, Suite 6	Metairie	Louisiana	United States	70006
12	Henry Ford Health System 2799 West Grand Boulevard	Detroit	Michigan	United States	48202
13	Minnesota Oncology Hematology, P.A. 910 East 26th Street, Suites 100 and 200	Minneapolis	Minnesota	United States	55404
14	Southern Nevada Cancer Research Foundation 601 S Rancho Drive	Las Vegas	Nevada	United States	89106
15	New York Oncology Hematology, P.C. 400 Patroon Creek Blvd, Suite 1	Albany	New York	United States	12206
16	Sanford Roger Maris Cancer Center - Fargo 801 Broadway North Route 1058	Fargo	North Dakota	United States	58122
17	Northwest Cancer Specialists, P.C. 265 N Broadway	Portland	Oregon	United States	97227
18	Penn State University Milton S. Hershey Medical Center 500 University Drive	Hershey	Pennsylvania	United States	17033
19	Hematology and Oncology Associates of SC, LLC 900 West Faris Rd, 3rd Floor	Greenville	South Carolina	United States	29605
20	Tennessee Oncology 250 20th Ave North	Nashville	Tennessee	United States	37203
21	Texas Oncology Bedford 1609 Hospital Parkway	Bedford	Texas	United States	76022
22	Texas Oncology, P.A. 3410 Worth Street, Suites 300 & 400	Dallas	Texas	United States	75246
23	Texas Oncology, P.A. - Denton 3720 South I-35 East	Denton	Texas	United States	76210
24	Oncology Consultants, P.A. 2130 W. Holcombe Blvd. 10th Floor	Houston	Texas	United States	77030
25	Texas Oncology, P.A. - McAllen 1901 South 2nd Street	McAllen	Texas	United States	78503-1298
26	Scott and White Memorial Hospital and Clinic 2401 South 31st Street	Temple	Texas	United States	76508
27	Texas Oncology, P.A. - Tyler 910 E. Houston St, Suite 100	Tyler	Texas	United States	75702
28	Texas Oncology - Waco 1700 W. Hwy. 6	Waco	Texas	United States	76712
29	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
30	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
31	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
32	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
33	Box Hill Hospital	Box Hill	Victoria	Australia	3128
34	Sunshine Hospital	St. Albans	Victoria	Australia	3021
35	Border Medical Oncology	Wodonga	Victoria	Australia	3690
36	Fiona Stanley Hospital	Subiaco	Western Australia	Australia	6008
37	OLV Ziekenhuis	Aalst		Belgium	9300
38	AZ Sint Lucas	Brugge		Belgium	8310
39	ULB Hopital Erasme	Bruxelles		Belgium	1070
40	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
41	UZ Antwerpen	Edegem		Belgium	2650
42	CHC Clinique StJospeh	Liege		Belgium	4000
43	CHU Sart Tilman	Liège		Belgium	4000
44	AZ Turnhout - Campus Sint-Elisabeth	Turnhout		Belgium	2300
45	Nemocnice Rudolfa a Stefanie Benesov, a. s.	Benesov		Czechia	256 01
46	Service d'Oncologie Médicale	Brest Cedex	Finistere	France	29609
47	Service d'Hépato-Gastro-Entérologie	La Roche S/ Yon Cedex 9	Vendee	France	85925
48	Centre Oscar Lambret	Lille		France	59020
49	Universitaetsklinikum Koeln	Koeln	Nordrhein Westfalen	Germany	50937
50	Schwerpunktpraxis für Haematologie und Onkologie	Magdeburg	Sachsen Anhalt	Germany	39104
51	Charite Universitaetsmedizin	Berlin		Germany	13353
52	Schwerpunktpraxis für Haematologie und OnkologieOnkologische Schwerpunktpraxis Eppendorf	Hamburg		Germany	20249
53	Leopoldina Krankenhaus	Schweinfurt		Germany	97422
54	A.O.U. Ospedali Riuniti Ancona- Clinica Oncologica	Torrette Di Ancona	Ancona	Italy	60126
55	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo	Torino	Italy	10060
56	Ospedale San Raffaele	Milano		Italy	20132
57	National Cancer Center	Goyang-Si	Gyeonggi-Do	Korea, Republic of	10408
58	Seoul National University Bundang Hospital	Seongnam-Si	Gyeonggi-do	Korea, Republic of	13620
59	Chonnam National University Hwasun Hospital	Hwasun-Gun	Jeollanam-Do	Korea, Republic of	58128
60	Kyungpook National University Medical Center	Daegu		Korea, Republic of	41404
61	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
62	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
63	Asan Medical Center	Seoul		Korea, Republic of	05505
64	Samsung Medical Center	Seoul		Korea, Republic of	06351
65	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
66	Seoul National Univ Hospital	Seoul		Korea, Republic of	3080
67	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warszawa		Poland	02-781
68	Hospital Univ Vall dHebron	Barcelona		Spain	08035
69	Hospital del Mar	Barcelona		Spain	8003
70	Hospital Clinic de Barcelona	Barselona		Spain	08036
71	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
72	Clinico San Carlos Hospital	Madrid		Spain	28040
73	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
74	Hospital Universitario la Paz - site 546	Madrid		Spain	28046
75	Hosp Univer Madrid Sanchinarro	Madrid		Spain	28050

Sponsors and Collaborators

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

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Mar 28, 2018
• Statistical Analysis Plan - Oct 12, 2017

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: NCT02625623
• Other Study ID Numbers: EMR 100070-008; 2015-003301-42
• First Posted: Dec 9, 2015
• Last Update Posted: Nov 24, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMD Serono Research & Development Institute, Inc.: Avelumab; Gastric cancer; Gastroesophageal junction adenocarcinoma
• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Paclitaxel; Irinotecan; Avelumab

Study Results

Participant Flow

Recruitment Details	Overall, 459 participants were screened for this study. Of which, 371 participants were randomized into the study.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	186	185
Treated	177	184
COMPLETED	177	184
NOT COMPLETED	9	1

Baseline Characteristics

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	186	185	371
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (12.93)	58.8 (11.66)	59.5 (12.31)
Sex: Female, Male (Count of Participants)
Female	59 31.7%	45 24.3%	104 28%
Male	127 68.3%	140 75.7%	267 72%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 8.1%	15 8.1%	30 8.1%
Not Hispanic or Latino	150 80.6%	153 82.7%	303 81.7%
Unknown or Not Reported	21 11.3%	17 9.2%	38 10.2%
Race/Ethnicity, Customized (Count of Participants)
White	117 62.9%	119 64.3%	236 63.6%
Black or African American	1 0.5%	1 0.5%	2 0.5%
Asian	47 25.3%	47 25.4%	94 25.3%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Not collected/Missing	19 10.2%	15 8.1%	34 9.2%
Other	2 1.1%	3 1.6%	5 1.3%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	From randomization up to 627 days

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	186	185
Median (95% Confidence Interval) [months]	5.0	4.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8078
	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	1.11
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
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). 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 up to 627 days

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	186	185
Median (95% Confidence Interval) [months]	2.7	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	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	1.73
	Confidence Interval	(2-Sided) 95%; 1.36 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Best Overall Response (BOR)
Description	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).
Time Frame	From randomization up to 627 days

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligram 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.
Measure Participants	186	185
Complete Response	1 0.5%	1 0.5%
Partial response	7 3.8%	3 1.6%
Stable disease	62 33.3%	30 16.2%
Non-complete response/ Non-progressive disease	12 6.5%	7 3.8%
Progressive disease	59 31.7%	94 50.8%
Non-evaluable	45 24.2%	50 27%

4. Secondary Outcome

Title	Objective Response Rate (ORR)
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 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.
Time Frame	From randomization up to 627 days

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + SC
Arm/Group Description	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.	Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligram 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.
Measure Participants	186	185
Number (95% Confidence Interval) [percentage of participants]	4.3 2.3%	2.2 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8764
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The treatment arms were compared by 1-sided CMH test. The stratification factor was region (Asia versus non Asia).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.709
	Confidence Interval	() %; to
	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 at End of Treatment (EOT)
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, EOT (up to Week 66)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	92	74
Mean (Standard Deviation) [units on a scale]	-0.103 (0.2113)	-0.144 (0.2088)

6. Secondary Outcome

Title	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)
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, EOT (up to Week 66)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	92	74
Mean (Standard Deviation) [millimeter (mm)]	-12.3 (19.22)	-13.6 (19.76)

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 at End of Treatment (EOT)
Description	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, EOT (up to Week 66)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	92	74
Mean (Standard Deviation) [units on a scale]	-10.14 (19.914)	-15.77 (19.437)

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 at End of Treatment (EOT)
Description	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.
Time Frame	Baseline, EOT (up to Week 66)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)	Avelumab + BSC
Arm/Group Description	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.	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.
Measure Participants	92	74
Dysphagia	7.25 (28.551)	15.32 (29.120)
Pain	8.88 (22.402)	9.23 (21.527)
Reflux	4.59 (20.184)	7.96 (18.347)
Eating Restrictions	9.24 (22.661)	13.29 (21.276)
Anxiety	7.49 (21.860)	6.61 (19.456)
Dry Mouth	15.94 (27.725)	9.01 (28.827)
Tasting	9.42 (25.832)	2.25 (35.897)
Body Image	5.07 (28.787)	4.05 (27.561)
Hair Loss	4.71 (33.546)	-13.96 (26.029)

Adverse Events

Time Frame	From randomization up to 627 days
Adverse Event Reporting Description	All participants who received at least 1 dose of study drug (that is, treated participants) were included in safety population.
Arm/Group Title	Physician Choice Chemotherapy + Best Supportive Care (BSC)		Avelumab + BSC
Arm/Group Description	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.		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.
All Cause Mortality
	Physician Choice Chemotherapy + Best Supportive Care (BSC)		Avelumab + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	131/177 (74%)		142/184 (77.2%)
Serious Adverse Events
	Physician Choice Chemotherapy + Best Supportive Care (BSC)		Avelumab + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/177 (45.8%)		90/184 (48.9%)
Blood and lymphatic system disorders
Anaemia	3/177 (1.7%)		5/184 (2.7%)
Febrile neutropenia	3/177 (1.7%)		0/184 (0%)
Disseminated intravascular coagulation	0/177 (0%)		1/184 (0.5%)
Lymphadenopathy mediastinal	0/177 (0%)		1/184 (0.5%)
Cardiac disorders
Cardio-respiratory arrest	0/177 (0%)		1/184 (0.5%)
Pericardial effusion	0/177 (0%)		1/184 (0.5%)
Cardiac arrest	1/177 (0.6%)		0/184 (0%)
Tachycardia	1/177 (0.6%)		0/184 (0%)
Endocrine disorders
Autoimmune hypothyroidism	0/177 (0%)		1/184 (0.5%)
Gastrointestinal disorders
Abdominal pain	1/177 (0.6%)		6/184 (3.3%)
Vomiting	1/177 (0.6%)		5/184 (2.7%)
Intestinal obstruction	1/177 (0.6%)		4/184 (2.2%)
Ascites	1/177 (0.6%)		3/184 (1.6%)
Dysphagia	1/177 (0.6%)		3/184 (1.6%)
Ileus	4/177 (2.3%)		2/184 (1.1%)
Subileus	3/177 (1.7%)		1/184 (0.5%)
Diarrhoea	3/177 (1.7%)		0/184 (0%)
Abdominal pain upper	0/177 (0%)		2/184 (1.1%)
Colitis	0/177 (0%)		1/184 (0.5%)
Constipation	1/177 (0.6%)		1/184 (0.5%)
Duodenal obstruction	0/177 (0%)		1/184 (0.5%)
Intestinal perforation	0/177 (0%)		1/184 (0.5%)
Nausea	2/177 (1.1%)		1/184 (0.5%)
Small intestinal obstruction	1/177 (0.6%)		1/184 (0.5%)
Gastric stenosis	1/177 (0.6%)		0/184 (0%)
Haematemesis	1/177 (0.6%)		0/184 (0%)
Haemorrhagic ascites	1/177 (0.6%)		0/184 (0%)
Melaena	1/177 (0.6%)		0/184 (0%)
General disorders
Disease progression	30/177 (16.9%)		39/184 (21.2%)
General physical health deterioration	3/177 (1.7%)		11/184 (6%)
Asthenia	2/177 (1.1%)		3/184 (1.6%)
Pain	0/177 (0%)		1/184 (0.5%)
Pyrexia	1/177 (0.6%)		1/184 (0.5%)
Chills	1/177 (0.6%)		0/184 (0%)
Condition aggravated	1/177 (0.6%)		0/184 (0%)
Fatigue	1/177 (0.6%)		0/184 (0%)
Multiple organ dysfunction syndrome	1/177 (0.6%)		0/184 (0%)
Oedema peripheral	2/177 (1.1%)		0/184 (0%)
Sudden death	1/177 (0.6%)		0/184 (0%)
Hepatobiliary disorders
Autoimmune hepatitis	0/177 (0%)		1/184 (0.5%)
Bile duct obstruction	0/177 (0%)		1/184 (0.5%)
Bile duct stone	0/177 (0%)		1/184 (0.5%)
Biliary dilatation	0/177 (0%)		1/184 (0.5%)
Hepatic failure	2/177 (1.1%)		1/184 (0.5%)
Hepatic function abnormal	0/177 (0%)		1/184 (0.5%)
Jaundice cholestatic	1/177 (0.6%)		1/184 (0.5%)
Cholangitis	1/177 (0.6%)		0/184 (0%)
Cholecystitis	1/177 (0.6%)		0/184 (0%)
Dilatation intrahepatic duct acquired	1/177 (0.6%)		0/184 (0%)
Infections and infestations
Pneumonia	2/177 (1.1%)		5/184 (2.7%)
Sepsis	2/177 (1.1%)		3/184 (1.6%)
Device related infection	1/177 (0.6%)		2/184 (1.1%)
Diverticulitis	0/177 (0%)		1/184 (0.5%)
Urinary tract infection	0/177 (0%)		1/184 (0.5%)
Abdominal infection	1/177 (0.6%)		0/184 (0%)
Device related sepsis	1/177 (0.6%)		0/184 (0%)
Empyema	1/177 (0.6%)		0/184 (0%)
Herpes zoster	2/177 (1.1%)		0/184 (0%)
Lung infection	1/177 (0.6%)		0/184 (0%)
Pulmonary sepsis	1/177 (0.6%)		0/184 (0%)
Respiratory tract infection bacterial	1/177 (0.6%)		0/184 (0%)
Septic shock	1/177 (0.6%)		0/184 (0%)
Injury, poisoning and procedural complications
Hip fracture	0/177 (0%)		1/184 (0.5%)
Infusion related reaction	0/177 (0%)		1/184 (0.5%)
Anastomotic stenosis	1/177 (0.6%)		0/184 (0%)
Investigations
Alanine aminotransferase increased	1/177 (0.6%)		1/184 (0.5%)
Aspartate aminotransferase increased	1/177 (0.6%)		1/184 (0.5%)
Liver function test increased	1/177 (0.6%)		1/184 (0.5%)
Platelet count decreased	0/177 (0%)		1/184 (0.5%)
Metabolism and nutrition disorders
Decreased appetite	4/177 (2.3%)		1/184 (0.5%)
Dehydration	3/177 (1.7%)		1/184 (0.5%)
Hyponatraemia	0/177 (0%)		2/184 (1.1%)
Malnutrition	1/177 (0.6%)		1/184 (0.5%)
Hyperuricaemia	1/177 (0.6%)		0/184 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/177 (0%)		2/184 (1.1%)
Exostosis	0/177 (0%)		1/184 (0.5%)
Osteonecrosis	1/177 (0.6%)		0/184 (0%)
Soft tissue disorder	1/177 (0.6%)		0/184 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa	0/177 (0%)		1/184 (0.5%)
Malignant ascites	0/177 (0%)		1/184 (0.5%)
Malignant neoplasm progression	0/177 (0%)		1/184 (0.5%)
Metastases to central nervous system	0/177 (0%)		1/184 (0.5%)
Metastases to spine	0/177 (0%)		1/184 (0.5%)
Neoplasm swelling	0/177 (0%)		1/184 (0.5%)
Pericarditis malignant	0/177 (0%)		1/184 (0.5%)
Tumour associated fever	0/177 (0%)		1/184 (0.5%)
Tumour pain	2/177 (1.1%)		1/184 (0.5%)
Neoplasm progression	1/177 (0.6%)		0/184 (0%)
Nervous system disorders
Dizziness	0/177 (0%)		2/184 (1.1%)
Product Issues
Device occlusion	0/177 (0%)		1/184 (0.5%)
Renal and urinary disorders
Hydronephrosis	0/177 (0%)		1/184 (0.5%)
Acute kidney injury	1/177 (0.6%)		0/184 (0%)
Renal failure	1/177 (0.6%)		0/184 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/177 (2.3%)		2/184 (1.1%)
Pneumonia aspiration	1/177 (0.6%)		2/184 (1.1%)
Pulmonary oedema	0/177 (0%)		1/184 (0.5%)
Respiratory failure	1/177 (0.6%)		1/184 (0.5%)
Pleural effusion	1/177 (0.6%)		0/184 (0%)
Pulmonary embolism	2/177 (1.1%)		0/184 (0%)
Respiratory distress	1/177 (0.6%)		0/184 (0%)
Vascular disorders
Deep vein thrombosis	1/177 (0.6%)		0/184 (0%)
Shock symptom	1/177 (0.6%)		0/184 (0%)
Other (Not Including Serious) Adverse Events
	Physician Choice Chemotherapy + Best Supportive Care (BSC)		Avelumab + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	150/177 (84.7%)		146/184 (79.3%)
Blood and lymphatic system disorders
Anaemia	48/177 (27.1%)		30/184 (16.3%)
Neutropenia	25/177 (14.1%)		0/184 (0%)
Gastrointestinal disorders
Nausea	61/177 (34.5%)		34/184 (18.5%)
Vomiting	32/177 (18.1%)		33/184 (17.9%)
Abdominal pain	31/177 (17.5%)		25/184 (13.6%)
Diarrhoea	54/177 (30.5%)		24/184 (13%)
Constipation	27/177 (15.3%)		18/184 (9.8%)
Dysphagia	2/177 (1.1%)		10/184 (5.4%)
Abdominal pain upper	18/177 (10.2%)		7/184 (3.8%)
General disorders
Fatigue	28/177 (15.8%)		28/184 (15.2%)
Asthenia	35/177 (19.8%)		26/184 (14.1%)
Pyrexia	30/177 (16.9%)		21/184 (11.4%)
Chills	3/177 (1.7%)		19/184 (10.3%)
Oedema peripheral	16/177 (9%)		5/184 (2.7%)
Injury, poisoning and procedural complications
Infusion related reaction	3/177 (1.7%)		18/184 (9.8%)
Investigations
Aspartate aminotransferase increased	13/177 (7.3%)		16/184 (8.7%)
Weight decreased	12/177 (6.8%)		16/184 (8.7%)
Gamma-glutamyltransferase increased	13/177 (7.3%)		15/184 (8.2%)
Blood alkaline phosphatase increased	10/177 (5.6%)		14/184 (7.6%)
Alanine aminotransferase increased	13/177 (7.3%)		11/184 (6%)
Neutrophil count decreased	16/177 (9%)		0/184 (0%)
White blood cell count decreased	14/177 (7.9%)		0/184 (0%)
Metabolism and nutrition disorders
Decreased appetite	37/177 (20.9%)		29/184 (15.8%)
Dehydration	3/177 (1.7%)		10/184 (5.4%)
Musculoskeletal and connective tissue disorders
Back pain	6/177 (3.4%)		18/184 (9.8%)
Nervous system disorders
Peripheral sensory neuropathy	14/177 (7.9%)		1/184 (0.5%)
Respiratory, thoracic and mediastinal disorders
Cough	10/177 (5.6%)		8/184 (4.3%)
Dyspnoea	15/177 (8.5%)		7/184 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	25/177 (14.1%)		0/184 (0%)

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.