Trial Outcomes & Findings for An Efficacy Study in Gastric and Gastroesophageal Junction Cancer Comparing Ipilimumab Versus Standard of Care Immediately Following First Line Chemotherapy (NCT NCT01585987)

Last Updated: 2016-05-17

Results Overview

irPFS is defined as the time between the randomization date and the time of disease progression per irRC or death, whichever occurs first. irRC criteria=Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%). New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. irPFS was measured in months.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

143 participants

Primary outcome timeframe

Randomization up to 91 irPFS events (Approximately 19 months )

Results posted on

2016-05-17

Participant Flow

Acceptable first-line chemotherapy before randomization to this study for a participant was a regimen containing a fluoropyrimidine agent and a platinum salt. Study initiated July 2012. Primary endpoint July 2014. Study completed April 2015.

114 enrolled and randomized. 29 enrolled but not randomized to treatment group: 26 no longer met study criteria; 2 withdrew consent, 1 other.

Participant milestones

Participant milestones
Measure	Ipilimumab Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	All Best Supportive Care (BSC) All BSC includes both active and non-active BSC. Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. In non-active BSC, the fluoropyrimidine used during lead-in chemotherapy was not continued on study and no other chemotherapy or active treatment was used
Randomized STARTED	57	57
Randomized COMPLETED	57	51
Randomized NOT COMPLETED	0	6
Treated STARTED	57	51
Treated COMPLETED	3	2
Treated NOT COMPLETED	54	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Ipilimumab Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	All Best Supportive Care (BSC) All BSC includes both active and non-active BSC. Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. In non-active BSC, the fluoropyrimidine used during lead-in chemotherapy was not continued on study and no other chemotherapy or active treatment was used
Randomized Withdrawal by Subject	0	4
Randomized No longer met criteria	0	2
Treated Disease Progression	39	36
Treated Study Drug Toxicity	9	5
Treated Adverse Event	3	0
Treated Withdrawal by Subject	1	2
Treated Death	1	0
Treated Lost to Follow-up	0	1
Treated Maximum Clinical Benefit	0	1
Treated Non-Specified	1	2
Treated Subject Request	0	1
Treated Poor/Non-Compliance	0	1

Baseline Characteristics

An Efficacy Study in Gastric and Gastroesophageal Junction Cancer Comparing Ipilimumab Versus Standard of Care Immediately Following First Line Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	All Best Supportive Care (BSC) n=57 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment.	Total n=114 Participants Total of all reporting groups
Age, Continuous	65.0 years n=93 Participants	62.0 years n=4 Participants	64.0 years n=27 Participants
Age, Customized Less than (<) 65 years of age	28 participants n=93 Participants	35 participants n=4 Participants	63 participants n=27 Participants
Age, Customized Greater, equal to (>=) 65 years of age	29 participants n=93 Participants	22 participants n=4 Participants	51 participants n=27 Participants
Sex: Female, Male Female	21 Participants n=93 Participants	16 Participants n=4 Participants	37 Participants n=27 Participants
Sex: Female, Male Male	36 Participants n=93 Participants	41 Participants n=4 Participants	77 Participants n=27 Participants
Region of Enrollment Russian Federation	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Singapore	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Hong Kong	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment United States	8 participants n=93 Participants	6 participants n=4 Participants	14 participants n=27 Participants
Region of Enrollment Japan	7 participants n=93 Participants	5 participants n=4 Participants	12 participants n=27 Participants
Region of Enrollment Taiwan	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Poland	0 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Korea, Republic of	21 participants n=93 Participants	24 participants n=4 Participants	45 participants n=27 Participants
Region of Enrollment Italy	11 participants n=93 Participants	8 participants n=4 Participants	19 participants n=27 Participants
Region of Enrollment France	3 participants n=93 Participants	5 participants n=4 Participants	8 participants n=27 Participants
Region of Enrollment Germany	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Spain	2 participants n=93 Participants	5 participants n=4 Participants	7 participants n=27 Participants

PRIMARY outcome

Timeframe: Randomization up to 91 irPFS events (Approximately 19 months )

Population: All participants who were randomized were summarized.

Outcome measures

Outcome measures
Measure	All Best Supportive Care (BSC) n=57 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.
Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines	4.8950 Months Interval 3.45 to 6.538	2.9240 Months Interval 1.61 to 5.158

SECONDARY outcome

Timeframe: Randomization up to 91 irPFS events (Approximately 19 months )

Population: All participants randomized to a treatment group were summarized.

PFS per mWHO was defined as the time between the randomization date and the time of disease progression per mWHO criteria or death, whichever occurred first and was measured in months. mWHO criteria: New lesions always mean progression; Changes in non-measurable lesions contribute in the definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD).

Outcome measures

Outcome measures
Measure	All Best Supportive Care (BSC) n=57 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.
Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria	4.8950 Months Interval 3.45 to 6.078	2.7270 Months Interval 1.446 to 2.957

SECONDARY outcome

Timeframe: Randomization up to 91 irPFS events (Approximately 19 months)

Population: All participants randomized to a treatment group and who received at least one dose of active drug were summarized.

OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	All Best Supportive Care (BSC) n=51 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.
Overall Survival (OS) at Primary Endpoint	12.0570 Months Interval 9.331 to Not estimable since the largest observation was censored.	16.7560 Months Interval 11.795 to 23.129

SECONDARY outcome

Timeframe: Randomization up to end of study, April 2015 (Approximately 28 months)

Population: All participants randomized to a treatment group and who received at least one dose of active drug were summarized.

OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	All Best Supportive Care (BSC) n=57 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.
Overall Survival (OS) at Study Completion	12.06 Months Interval 9.33 to Upper limit was not estimable.	12.68 Months Interval 10.51 to 18.92

SECONDARY outcome

Timeframe: Randomization up to 91 irPFS events (Approximately 19 months)

Population: All participants randomized to a treatment group were summarized.

IrBOR rate was defined as the number of participants whose Immune-related Best Overall Response (irBOR) criteria was Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR), divided by the total number of participants. The immune-related sum of products of diameters (irSPD) incorporates - in addition to the index lesions - measurable new lesions that may have developed on-study, providing an assessment that includes both index and new lesions. irCR=Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR=A 50% or greater decrease, relative to baseline of the irSPD, (based on irSPD of all index lesions and any measurable new lesions).

Outcome measures

Outcome measures
Measure	All Best Supportive Care (BSC) n=57 Participants BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. All BSC = Active and non-active BSC.	Ipilimumab n=57 Participants Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.
Percentage of Participants With Immune-Related Best Overall Response (irBOR)	7.0 percentage of participants	1.8 percentage of participants

Adverse Events

Ipilimumab

Serious events: 31 serious events

Other events: 55 other events

Deaths: 0 deaths

Active Best Supportive Care (BSC)

Serious events: 19 serious events

Other events: 42 other events

Deaths: 0 deaths

Non-Active BSC

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ipilimumab n=57 participants at risk Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	Active Best Supportive Care (BSC) n=45 participants at risk Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization)	Non-Active BSC n=6 participants at risk Non-Active BSC involves supportive care with cessation of chemotherapy (no active drug)
Gastrointestinal disorders Abdominal pain	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Renal and urinary disorders Acute kidney injury	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Decreased appetite	12.3% 7/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Dysphagia	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Hypoglycaemia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Intestinal obstruction	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Pyrexia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Transaminases increased	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Dehydration	3.5% 2/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Endocrine disorders Hypopituitarism	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Musculoskeletal and connective tissue disorders Myalgia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Obstruction gastric	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Cardiac disorders Acute coronary syndrome	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Hepatobiliary disorders Cholecystocholangitis	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Colitis ischaemic	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Nervous system disorders Dizziness	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Renal and urinary disorders Haematuria	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Hypokalaemia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Endocrine disorders Hypothyroidism	3.5% 2/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Nervous system disorders Peripheral sensory neuropathy	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Infections and infestations Pneumocystis jirovecii pneumonia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Nervous system disorders Syncope	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Cardiac disorders Cardio-respiratory arrest	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Vascular disorders Deep vein thrombosis	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Dyspepsia	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Failure to thrive	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Hyponatraemia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Hypothermia	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Performance status decreased	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Infections and infestations Peritonitis	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Infections and infestations Urinary tract infection	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Musculoskeletal and connective tissue disorders Back pain	3.5% 2/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Death	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Infections and infestations Device related infection	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Disease progression	10.5% 6/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Endocrine disorders Endocrine disorder	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders General physical health deterioration	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015

Other adverse events
Measure	Ipilimumab n=57 participants at risk Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met.	Active Best Supportive Care (BSC) n=45 participants at risk Active BSC includes the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization)	Non-Active BSC n=6 participants at risk Non-Active BSC involves supportive care with cessation of chemotherapy (no active drug)
Gastrointestinal disorders Abdominal pain	21.1% 12/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	35.6% 16/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Alanine aminotransferase increased	15.8% 9/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Decreased appetite	36.8% 21/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	31.1% 14/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Dysphagia	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	33.3% 2/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Hiccups	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Productive cough	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Pyrexia	15.8% 9/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	15.6% 7/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.5% 6/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	11.1% 5/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Musculoskeletal and connective tissue disorders Myalgia	7.0% 4/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Pain	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	7.0% 4/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	17.8% 8/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Pruritus	43.9% 25/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	6.7% 3/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Abdominal pain upper	10.5% 6/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Aspartate aminotransferase increased	15.8% 9/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Constipation	17.5% 10/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	26.7% 12/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Nervous system disorders Dizziness	8.8% 5/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Hypokalaemia	14.0% 8/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Endocrine disorders Hypothyroidism	7.0% 4/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Injury, poisoning and procedural complications Laceration	1.8% 1/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Nervous system disorders Peripheral sensory neuropathy	10.5% 6/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Rash	26.3% 15/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Weight decreased	19.3% 11/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	11.1% 5/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Dyspepsia	8.8% 5/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	6.7% 3/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Metabolism and nutrition disorders Hyponatraemia	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Nausea	33.3% 19/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	35.6% 16/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Blood and lymphatic system disorders Neutropenia	3.5% 2/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	15.6% 7/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Musculoskeletal and connective tissue disorders Back pain	10.5% 6/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	6.7% 3/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Dry skin	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Influenza like illness	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	6.7% 3/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Gastrointestinal disorders Vomiting	29.8% 17/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	26.7% 12/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Skin and subcutaneous tissue disorders Alopecia	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	4.4% 2/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Haemoglobin decreased	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Investigations Weight increased	5.3% 3/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	2.2% 1/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	16.7% 1/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Blood and lymphatic system disorders Anaemia	21.1% 12/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	11.1% 5/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
Psychiatric disorders Anxiety	0.00% 0/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	8.9% 4/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015
General disorders Asthenia	21.1% 12/57 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	15.6% 7/45 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015	0.00% 0/6 • Randomization to end of study (April 2015) Study initiated: July 2012; End of Study: April 2015