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Clinical Trial Results:
An Open-Label Exploratory Phase 2/3 Study of Nivolumab with Standard of Care Therapy vs Standard of Care Therapy for First-Line Treatment of Metastatic Colorectal Cancer (CheckMate 9X8: CHECKpoint pathway and nivoluMab clinical Trial Evaluation 9X8)

Summary
EudraCT number	2017-003662-27
Trial protocol	ES
Global end of trial date	28 Dec 2022

Results information
Results version number	v1(current)
This version publication date	12 Nov 2023
First version publication date	12 Nov 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CA209-9X8

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussee de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Feb 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Dec 2022

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of nivolumab plus standard of care (SOC) chemotherapy with bevacizumab (Nivo + SOC) with SOC chemotherapy with bevacizumab in participants with mCRC

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Feb 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 19

Country: Number of subjects enrolled

Japan: 17

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

United States: 144

Worldwide total number of subjects

195

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

136

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

195 participants randomized and 185 participants treated

Period 1 title

Pre-Treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Arm A: NIV+mFOLFOX+BEV

Arm description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

240 mg IV every 2 weeks

Investigational medicinal product name

Bevacizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg/kg IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg/m2 continuous infusion every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

350 mg/m2 IV every 2 weeks

Investigational medicinal product name

Oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

85 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg/m2 continuous infusion every 2 weeks

Arm B: mFOLFOX+BEV

Arm description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Arm type

Experimental

Investigational medicinal product name

Bevacizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg/kg IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg/m2 continuous infusion every 2 weeks

Investigational medicinal product name

Oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

85 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

350 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg/m2 continuous infusion every 2 weeks

Number of subjects in period 1	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Started	127	68
Completed	123	62
Not completed	4	6
Participant withdrew consent	1	3
Participant no longer meets study criteria	2	3
Other reasons	1	-

Period 2 title

Treatment

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Arm A: NIV+mFOLFOX+BEV

Arm description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

240 mg IV every 2 weeks

Investigational medicinal product name

Bevacizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg/kg IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

350 mg/m2 IV every 2 weeks

Investigational medicinal product name

Oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

85 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Arm B: mFOLFOX+BEV

Arm description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Arm type

Experimental

Investigational medicinal product name

Bevacizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg/kg IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

1200 mg/m2 IV every 2 weeks

Investigational medicinal product name

Oxaliplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

85 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

400 mg/m2 IV every 2 weeks

Investigational medicinal product name

Leucovorin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

350 mg/m2 IV every 2 weeks

Investigational medicinal product name

Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

2400 mg/m2 IV every 2 weeks

Number of subjects in period 2	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Started	123	62
Completed	9	0
Not completed	114	62
Adverse event, serious fatal	-	1
Participant withdrew consent	4	3
Not reported	1	-
Maximum clinical benefit	5	9
Adverse Event Unrelated to Study Drug	5	2
Other reasons	3	2
Study Drug Toxicity	10	5
Lost to follow-up	-	1
Poor/non-compliance	2	-
Administrative reasons by sponsor	1	-
Disease Progression	75	29
Participant request to discontinue study treatment	8	10

Baseline characteristics

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Reporting group title

Arm A: NIV+mFOLFOX+BEV

Reporting group description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Reporting group title

Arm B: mFOLFOX+BEV

Reporting group description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Reporting group values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV	Total
Number of subjects	127	68	195
Age categorical
Units: Subjects
Adults (18-64 years)	89	47	136
From 65-84 years	28	18	46
85 years and over	10	3	13
Age Continuous
Units: Years
arithmetic mean (standard deviation)	56.8 ( 13.3 )	57.2 ( 11.4 )	-
Sex: Female, Male
Units: Participants
Female	57	19	76
Male	70	49	119
Race/Ethnicity, Customized
Units: Subjects
White	96	57	153
Black or African American	8	2	10
Asian	15	5	20
Other	6	3	9
Not Reported	2	1	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	7	9	16
Not Hispanic or Latino	108	53	161
Unknown or Not Reported	12	6	18

End points

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Reporting group title

Arm A: NIV+mFOLFOX+BEV

Reporting group description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Reporting group title

Arm B: mFOLFOX+BEV

Reporting group description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Reporting group title

Arm A: NIV+mFOLFOX+BEV

Reporting group description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Reporting group title

Arm B: mFOLFOX+BEV

Reporting group description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Primary: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR)

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End point title

Progression Free Survival (PFS) per Blinded Independent Central Review (BICR)

End point description

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by BICR (per RECIST 1.1), or death due to any cause, whichever occurs first. Baseline tumor assessment is defined as tumor scans prior to or on randomization date. Participants who did not have documented progression per BICR and who did not die or participants who started any subsequent anti-cancer therapy without a prior reported progression per BICR will be censored at the date of the last tumor assessment on or prior to initiation of the subsequent anticancer therapy, if any. Participants who die without a reported prior progression per BICR will be considered to have progressed on the date of death. Participants who did not have any baseline or post baseline tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date.

End point type

Primary

End point timeframe

From randomization to up to the date of the first documented progression (up to 16 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Months
median (confidence interval 95%)	11.86 (8.94 to 15.70)	11.93 (10.09 to 12.19)

PFS

Statistical analysis description

Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV

Comparison groups

Arm A: NIV+mFOLFOX+BEV v Arm B: mFOLFOX+BEV

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

P-value

= 0.3022 ^[1]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.23

Notes
[1] - Stratified regular log-rank test

PFS

Statistical analysis description

Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV

Comparison groups

Arm A: NIV+mFOLFOX+BEV v Arm B: mFOLFOX+BEV

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

P-value

= 0.3022 ^[2]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

80%

sides

2-sided

lower limit

0.61

upper limit

1.07

Notes
[2] - Stratified regular log-rank test

Secondary: Objective Response Rate (ORR) per Investigator Assessment

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End point title

Objective Response Rate (ORR) per Investigator Assessment

End point description

ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). BOR is defined as the best response designation as determined by tumor assessments by the Investigator per RECIST 1.1, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.

End point type

Secondary

End point timeframe

From the date of randomization up to the date of objectively documented progression or the date of subsequent anticancer therapy, whichever occurs first (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Percentage of participants
number (confidence interval 95%)	60.6 (51.6 to 69.2)	52.9 (40.4 to 65.2)

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

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End point title

Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

End point description

ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). BOR is defined as the best response designation as determined by BICR per RECIST 1.1, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.

End point type

Secondary

End point timeframe

From the date of randomization up to the date of objectively documented progression or the date of subsequent anticancer therapy, whichever occurs first (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Percentage of Participants
number (confidence interval 95%)	60.6 (51.6 to 69.2)	45.6 (33.5 to 58.1)

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS) per Investigator Assessment

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End point title

Progression Free Survival (PFS) per Investigator Assessment

End point description

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by Investigator Assessment, or death due to any cause, whichever occurs first. Baseline tumor assessment is defined as tumor scans prior to or on randomization date. Participants who did not have documented progression per Investigator Assessment and who did not die or participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the date of the last tumor assessment on or prior to initiation of the subsequent anticancer therapy, if any. Participants who die without a reported prior progression per Investigator Assessment will be considered to have progressed on the date of death. Participants who did not have any baseline or post baseline tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date.

End point type

Secondary

End point timeframe

From randomization up to the date of the first documented progression (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Months
median (confidence interval 95%)	13.77 (11.53 to 15.70)	12.19 (10.25 to 14.06)

PFS

Statistical analysis description

Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV

Comparison groups

Arm A: NIV+mFOLFOX+BEV v Arm B: mFOLFOX+BEV

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.19

Secondary: Time to Objective Response per Blinded Independent Central Review (BICR)

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End point title

Time to Objective Response per Blinded Independent Central Review (BICR)

End point description

Time to objective response (TTR) is defined as the time from the randomization date to the date of the first confirmed complete response (CR) or partial response (PR) as assessed by BICR. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm. TTR is derived for responders only.

End point type

Secondary

End point timeframe

From the randomization date up to the date of the first confirmed CR or PR (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	77	31
Units: Months
median (standard deviation)	2.83 ( 1.51 )	2.83 ( 1.45 )

No statistical analyses for this end point

Secondary: Time to Objective Response per Investigator Assessment

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End point title

Time to Objective Response per Investigator Assessment

End point description

TTR is defined as the time from the randomization date to the date of the first confirmed complete response (CR) or partial response (PR) as assessed by investigator. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm. TTR is derived for responders only.

End point type

Secondary

End point timeframe

From the randomization date up to the date of the first confirmed CR or PR (up to 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	77	36
Units: Months
median (standard deviation)	2.83 ( 2.51 )	2.83 ( 1.34 )

No statistical analyses for this end point

Secondary: Duration of Response (DoR) per Blinded Independent Central Review (BICR)

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End point title

Duration of Response (DoR) per Blinded Independent Central Review (BICR)

End point description

Duration of objective response (DoR) is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression as assessed by the BICR based on RECIST 1.1 criteria or death due to any cause, whichever occurs first. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.

End point type

Secondary

End point timeframe

From randomization up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	77	31
Units: Months
median (confidence interval 95%)	12.88 (9.00 to 14.72)	9.26 (7.49 to 11.30)

No statistical analyses for this end point

Secondary: Number of Participants With Adverse Events (AEs)

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End point title

Number of Participants With Adverse Events (AEs)

End point description

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

End point type

Secondary

End point timeframe

From first dose to 30 days post last dose (up to 45 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	123	62
Units: Participants
Any Grade	122	61

No statistical analyses for this end point

Secondary: Duration of Response (DoR) per Investigator Assessment

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End point title

Duration of Response (DoR) per Investigator Assessment

End point description

Duration of objective response (DoR) is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression as assessed by the investigator based on RECIST 1.1 criteria or death due to any cause, whichever occurs first. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. CR is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.

End point type

Secondary

End point timeframe

From randomization up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	77	36
Units: Months
median (confidence interval 95%)	12.48 (8.87 to 16.72)	11.07 (9.43 to 17.31)

No statistical analyses for this end point

Secondary: Number of Participants With Serious Adverse Events (SAEs)

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End point title

Number of Participants With Serious Adverse Events (SAEs)

End point description

Number of participants with any grade of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine safety and tolerability. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.

End point type

Secondary

End point timeframe

From first dose to 30 days post last dose (up to 45 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	123	62
Units: Participants	57	20

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) per Investigator

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End point title

Disease Control Rate (DCR) per Investigator

End point description

Disease Control Rate (DCR) is defined as the percentage of participants whose Best Overall Response (BOR) is complete response (CR) or partial response (PR) or stable disease (SD). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

End point type

Secondary

End point timeframe

From the date of randomization up to the date of objectively documented progression or the date of subsequent anticancer therapy, whichever occurs first (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Percentage of participants
number (confidence interval 95%)	85.8 (85.0 to 95.6)	77.9 (66.2 to 87.1)

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) per Blinded Independent Central Review (BICR)

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End point title

Disease Control Rate (DCR) per Blinded Independent Central Review (BICR)

End point description

End point type

Secondary

End point timeframe

From the date of randomization up to the date of objectively documented progression or the date of subsequent anticancer therapy, whichever occurs first (up to approximately 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Percentage of participants
number (confidence interval 95%)	91.3 (85.0 to 95.6)	83.8 (72.9 to 91.6)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.

End point type

Secondary

End point timeframe

From the date of randomization up to the date of death (up to 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Months
median (confidence interval 95%)	30.52 (25.20 to 39.39)	31.77 (24.38 to 38.70)

No statistical analyses for this end point

Secondary: Number of Participants Experiencing Death

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End point title

Number of Participants Experiencing Death

End point description

The number of participants who died during the treatment period

End point type

Secondary

End point timeframe

From first dose up to 6 weeks post last dose (up to 46 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	123	62
Units: Participants	87	42

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Liver Tests

End point description

The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal

End point type

Secondary

End point timeframe

From first dose up to 30 days post last dose (up to 45 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	123	62
Units: Participants
ALT OR AST > 3XULN	16	6
ALT OR AST > 5XULN	7	2
ALT OR AST > 10XULN	2	0
ALT OR AST > 20XULN	0	0
TOTAL BILIRUBIN > 2XULN	0	1
ALP > 1.5XULN	39	20
ALT/AST ELEV.>3XULN & TOT. BILIRUBIN>1.5XULN 1 DAY	2	1
ALT/AST ELEV>3XULN &TOT. BILIRUBIN>1.5XULN 30 DAYS	2	1
ALT/AST ELEV.>3XULN & TOT. BILIRUBIN>2XULN 1 DAY	0	1
ALT/AST ELEV.>3XULN & TOT. BILIRUBIN>2XULN 30 DAYS	0	1

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

End point description

The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal

End point type

Secondary

End point timeframe

From first dose up to 30 days post last dose (up to 45 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	123	60
Units: Participants
TSH > ULN	45	23
TSH > ULN WITH TSH <= ULN AT BASELINE	37	16
TSH > ULN WITH AT LEAST 1 FT3/FT4 TEST VALUE<LLN	20	2
TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES>=LLN	11	9
TSH > ULN WITH FT3/FT4 TEST MISSING	14	12
TSH < LLN	25	3
TSH < LLN WITH TSH >= LLN AT BASELINE	22	3
TSH < LLN WITH AT LEAST 1 FT3/FT4 TEST VALUE>ULN	13	0
TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES<=ULN	8	2
TSH < LLN WITH FT3/FT4 TEST MISSING	4	1

No statistical analyses for this end point

Post-hoc: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR) - Extended Collection

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End point title

Progression Free Survival (PFS) per Blinded Independent Central Review (BICR) - Extended Collection

End point description

PFS is the time from randomization to the date of first documented progression, as determined by BICR, or death due to any cause, whichever occurs first. Baseline tumor assessment is defined as tumor scans prior to or on randomization date. Participants who did not have documented progression and did not die or participants who started any subsequent anti-cancer therapy without a prior reported progression were censored on date of last tumor assessment on or prior to initiation of the subsequent anticancer therapy, if any. Participants who died without prior progression were considered to have progressed on the date of death. Participants who did not have any baseline assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) were censored at the randomization date. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.

End point type

Post-hoc

End point timeframe

From randomization to up to the date of the first documented progression (up to 44 months)

End point values	Arm A: NIV+mFOLFOX+BEV	Arm B: mFOLFOX+BEV
Number of subjects analysed	127	68
Units: Months
median (confidence interval 95%)	11.99 (9.99 to 15.74)	12.02 (10.25 to 13.37)

PFS

Statistical analysis description

Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV

Comparison groups

Arm A: NIV+mFOLFOX+BEV v Arm B: mFOLFOX+BEV

Number of subjects included in analysis

195

Analysis specification

Post-hoc

Analysis type

P-value

= 0.5041 ^[3]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

80%

sides

2-sided

lower limit

0.67

upper limit

1.15

Notes
[3] - Stratified regular log-rank test

PFS

Statistical analysis description

Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV

Comparison groups

Arm A: NIV+mFOLFOX+BEV v Arm B: mFOLFOX+BEV

Number of subjects included in analysis

195

Analysis specification

Post-hoc

Analysis type

P-value

= 0.5041 ^[4]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.32

Notes
[4] - Stratified regular log-rank test

Adverse events

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Timeframe for reporting adverse events

Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 58 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 45 months)

Adverse event reporting additional description

The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

mFOLFOX+BEV

Reporting group description

mFOLFOX6/bevacizumab (SOC) every 2 weeks

Reporting group title

NIV+mFOLFOX+BEV

Reporting group description

Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks

Serious adverse events	mFOLFOX+BEV	NIV+mFOLFOX+BEV
Total subjects affected by serious adverse events
subjects affected / exposed	25 / 62 (40.32%)	67 / 123 (54.47%)
number of deaths (all causes)	42	87
number of deaths resulting from adverse events	8	13
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer metastatic
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	1 / 62 (1.61%)	6 / 123 (4.88%)
occurrences causally related to treatment / all	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 6
Metastases to ovary
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to lung
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Orthostatic hypotension
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Death
subjects affected / exposed	2 / 62 (3.23%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 2
Infusion site extravasation
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 62 (1.61%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 62 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Pneumothorax
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	2 / 62 (3.23%)	6 / 123 (4.88%)
occurrences causally related to treatment / all	1 / 2	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood potassium increased
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal anastomotic leak
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stoma prolapse
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Myocarditis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Myocardial infarction
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intracardiac thrombus
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 1
Tachycardia
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Depressed level of consciousness
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Syncope
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	1 / 62 (1.61%)	6 / 123 (4.88%)
occurrences causally related to treatment / all	1 / 1	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Autoimmune haemolytic anaemia
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 62 (0.00%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune-mediated enterocolitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 62 (1.61%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	2 / 62 (3.23%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	1 / 2	0 / 0
Large intestinal obstruction
subjects affected / exposed	1 / 62 (1.61%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	1 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 62 (0.00%)	9 / 123 (7.32%)
occurrences causally related to treatment / all	0 / 0	11 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Ascites
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	3 / 62 (4.84%)	5 / 123 (4.07%)
occurrences causally related to treatment / all	1 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 62 (0.00%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 62 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal perforation
subjects affected / exposed	0 / 62 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 62 (0.00%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 62 (0.00%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal obstruction
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic lesion
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Autoimmune hepatitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal infection
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess neck
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	1 / 62 (1.61%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis bacterial
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 62 (0.00%)	4 / 123 (3.25%)
occurrences causally related to treatment / all	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia pseudomonal
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 62 (1.61%)	6 / 123 (4.88%)
occurrences causally related to treatment / all	0 / 1	3 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 62 (1.61%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spontaneous bacterial peritonitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Norovirus infection
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 62 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 62 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	mFOLFOX+BEV	NIV+mFOLFOX+BEV
Total subjects affected by non serious adverse events
subjects affected / exposed	61 / 62 (98.39%)	122 / 123 (99.19%)
Vascular disorders
Hypertension
subjects affected / exposed	12 / 62 (19.35%)	40 / 123 (32.52%)
occurrences all number	17	55
General disorders and administration site conditions
Asthenia
subjects affected / exposed	6 / 62 (9.68%)	22 / 123 (17.89%)
occurrences all number	11	34
Chills
subjects affected / exposed	1 / 62 (1.61%)	17 / 123 (13.82%)
occurrences all number	1	21
Fatigue
subjects affected / exposed	38 / 62 (61.29%)	73 / 123 (59.35%)
occurrences all number	47	99
Influenza like illness
subjects affected / exposed	1 / 62 (1.61%)	10 / 123 (8.13%)
occurrences all number	2	10
Malaise
subjects affected / exposed	3 / 62 (4.84%)	7 / 123 (5.69%)
occurrences all number	3	7
Mucosal inflammation
subjects affected / exposed	12 / 62 (19.35%)	15 / 123 (12.20%)
occurrences all number	14	20
Non-cardiac chest pain
subjects affected / exposed	4 / 62 (6.45%)	5 / 123 (4.07%)
occurrences all number	5	5
Oedema peripheral
subjects affected / exposed	2 / 62 (3.23%)	12 / 123 (9.76%)
occurrences all number	2	14
Pain
subjects affected / exposed	3 / 62 (4.84%)	8 / 123 (6.50%)
occurrences all number	3	11
Pyrexia
subjects affected / exposed	10 / 62 (16.13%)	35 / 123 (28.46%)
occurrences all number	13	53
Temperature intolerance
subjects affected / exposed	14 / 62 (22.58%)	32 / 123 (26.02%)
occurrences all number	16	35
Immune system disorders
Hypersensitivity
subjects affected / exposed	2 / 62 (3.23%)	10 / 123 (8.13%)
occurrences all number	4	12
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	4 / 62 (6.45%)	7 / 123 (5.69%)
occurrences all number	5	7
Nasal congestion
subjects affected / exposed	3 / 62 (4.84%)	8 / 123 (6.50%)
occurrences all number	5	14
Hiccups
subjects affected / exposed	6 / 62 (9.68%)	5 / 123 (4.07%)
occurrences all number	7	6
Epistaxis
subjects affected / exposed	13 / 62 (20.97%)	39 / 123 (31.71%)
occurrences all number	15	43
Dyspnoea
subjects affected / exposed	3 / 62 (4.84%)	26 / 123 (21.14%)
occurrences all number	3	32
Dysphonia
subjects affected / exposed	6 / 62 (9.68%)	16 / 123 (13.01%)
occurrences all number	6	17
Cough
subjects affected / exposed	10 / 62 (16.13%)	29 / 123 (23.58%)
occurrences all number	12	33
Rhinorrhoea
subjects affected / exposed	5 / 62 (8.06%)	9 / 123 (7.32%)
occurrences all number	6	10
Psychiatric disorders
Insomnia
subjects affected / exposed	10 / 62 (16.13%)	33 / 123 (26.83%)
occurrences all number	10	37
Depression
subjects affected / exposed	3 / 62 (4.84%)	13 / 123 (10.57%)
occurrences all number	3	14
Anxiety
subjects affected / exposed	2 / 62 (3.23%)	13 / 123 (10.57%)
occurrences all number	2	14
Investigations
Alanine aminotransferase increased
subjects affected / exposed	11 / 62 (17.74%)	19 / 123 (15.45%)
occurrences all number	12	32
Aspartate aminotransferase increased
subjects affected / exposed	10 / 62 (16.13%)	27 / 123 (21.95%)
occurrences all number	13	43
Blood alkaline phosphatase increased
subjects affected / exposed	5 / 62 (8.06%)	15 / 123 (12.20%)
occurrences all number	5	23
Blood creatinine increased
subjects affected / exposed	2 / 62 (3.23%)	11 / 123 (8.94%)
occurrences all number	3	19
Neutrophil count decreased
subjects affected / exposed	12 / 62 (19.35%)	39 / 123 (31.71%)
occurrences all number	46	86
Platelet count decreased
subjects affected / exposed	10 / 62 (16.13%)	25 / 123 (20.33%)
occurrences all number	20	52
Weight decreased
subjects affected / exposed	12 / 62 (19.35%)	18 / 123 (14.63%)
occurrences all number	14	19
White blood cell count decreased
subjects affected / exposed	5 / 62 (8.06%)	15 / 123 (12.20%)
occurrences all number	32	38
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 62 (1.61%)	11 / 123 (8.94%)
occurrences all number	1	11
Infusion related reaction
subjects affected / exposed	5 / 62 (8.06%)	27 / 123 (21.95%)
occurrences all number	6	41
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 62 (1.61%)	7 / 123 (5.69%)
occurrences all number	1	8
Nervous system disorders
Taste disorder
subjects affected / exposed	2 / 62 (3.23%)	8 / 123 (6.50%)
occurrences all number	3	8
Peripheral sensory neuropathy
subjects affected / exposed	28 / 62 (45.16%)	45 / 123 (36.59%)
occurrences all number	29	49
Paraesthesia
subjects affected / exposed	5 / 62 (8.06%)	11 / 123 (8.94%)
occurrences all number	5	13
Neurotoxicity
subjects affected / exposed	2 / 62 (3.23%)	12 / 123 (9.76%)
occurrences all number	5	16
Neuropathy peripheral
subjects affected / exposed	21 / 62 (33.87%)	54 / 123 (43.90%)
occurrences all number	25	76
Hypoaesthesia
subjects affected / exposed	6 / 62 (9.68%)	4 / 123 (3.25%)
occurrences all number	6	4
Headache
subjects affected / exposed	6 / 62 (9.68%)	25 / 123 (20.33%)
occurrences all number	6	40
Dysgeusia
subjects affected / exposed	12 / 62 (19.35%)	25 / 123 (20.33%)
occurrences all number	12	26
Dizziness
subjects affected / exposed	9 / 62 (14.52%)	22 / 123 (17.89%)
occurrences all number	9	25
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	7 / 62 (11.29%)	26 / 123 (21.14%)
occurrences all number	10	33
Neutropenia
subjects affected / exposed	14 / 62 (22.58%)	45 / 123 (36.59%)
occurrences all number	18	81
Anaemia
subjects affected / exposed	12 / 62 (19.35%)	32 / 123 (26.02%)
occurrences all number	29	46
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	3 / 62 (4.84%)	12 / 123 (9.76%)
occurrences all number	3	13
Abdominal pain
subjects affected / exposed	19 / 62 (30.65%)	40 / 123 (32.52%)
occurrences all number	26	51
Abdominal distension
subjects affected / exposed	2 / 62 (3.23%)	7 / 123 (5.69%)
occurrences all number	2	10
Colitis
subjects affected / exposed	1 / 62 (1.61%)	7 / 123 (5.69%)
occurrences all number	1	12
Vomiting
subjects affected / exposed	13 / 62 (20.97%)	49 / 123 (39.84%)
occurrences all number	14	87
Toothache
subjects affected / exposed	4 / 62 (6.45%)	5 / 123 (4.07%)
occurrences all number	4	8
Stomatitis
subjects affected / exposed	18 / 62 (29.03%)	28 / 123 (22.76%)
occurrences all number	19	40
Proctalgia
subjects affected / exposed	2 / 62 (3.23%)	12 / 123 (9.76%)
occurrences all number	2	18
Nausea
subjects affected / exposed	35 / 62 (56.45%)	83 / 123 (67.48%)
occurrences all number	51	152
Haemorrhoids
subjects affected / exposed	4 / 62 (6.45%)	6 / 123 (4.88%)
occurrences all number	5	7
Gastrooesophageal reflux disease
subjects affected / exposed	5 / 62 (8.06%)	7 / 123 (5.69%)
occurrences all number	5	7
Dyspepsia
subjects affected / exposed	6 / 62 (9.68%)	15 / 123 (12.20%)
occurrences all number	7	15
Diarrhoea
subjects affected / exposed	20 / 62 (32.26%)	74 / 123 (60.16%)
occurrences all number	32	149
Constipation
subjects affected / exposed	21 / 62 (33.87%)	52 / 123 (42.28%)
occurrences all number	29	80
Dry mouth
subjects affected / exposed	3 / 62 (4.84%)	15 / 123 (12.20%)
occurrences all number	3	18
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	6 / 62 (9.68%)	10 / 123 (8.13%)
occurrences all number	6	10
Skin hyperpigmentation
subjects affected / exposed	4 / 62 (6.45%)	9 / 123 (7.32%)
occurrences all number	4	10
Rash maculo-papular
subjects affected / exposed	0 / 62 (0.00%)	11 / 123 (8.94%)
occurrences all number	0	14
Rash
subjects affected / exposed	4 / 62 (6.45%)	14 / 123 (11.38%)
occurrences all number	5	17
Pruritus
subjects affected / exposed	2 / 62 (3.23%)	13 / 123 (10.57%)
occurrences all number	3	16
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	8 / 62 (12.90%)	14 / 123 (11.38%)
occurrences all number	8	16
Dry skin
subjects affected / exposed	6 / 62 (9.68%)	17 / 123 (13.82%)
occurrences all number	6	17
Renal and urinary disorders
Proteinuria
subjects affected / exposed	9 / 62 (14.52%)	18 / 123 (14.63%)
occurrences all number	21	33
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	1 / 62 (1.61%)	7 / 123 (5.69%)
occurrences all number	1	7
Hypothyroidism
subjects affected / exposed	1 / 62 (1.61%)	21 / 123 (17.07%)
occurrences all number	1	22
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	3 / 62 (4.84%)	21 / 123 (17.07%)
occurrences all number	3	21
Myalgia
subjects affected / exposed	3 / 62 (4.84%)	10 / 123 (8.13%)
occurrences all number	4	10
Arthralgia
subjects affected / exposed	9 / 62 (14.52%)	37 / 123 (30.08%)
occurrences all number	12	46
Back pain
subjects affected / exposed	9 / 62 (14.52%)	24 / 123 (19.51%)
occurrences all number	12	29
Bone pain
subjects affected / exposed	4 / 62 (6.45%)	5 / 123 (4.07%)
occurrences all number	4	5
Muscle spasms
subjects affected / exposed	0 / 62 (0.00%)	10 / 123 (8.13%)
occurrences all number	0	13
Muscular weakness
subjects affected / exposed	3 / 62 (4.84%)	11 / 123 (8.94%)
occurrences all number	3	12
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	6 / 62 (9.68%)	17 / 123 (13.82%)
occurrences all number	7	23
Urinary tract infection
subjects affected / exposed	7 / 62 (11.29%)	14 / 123 (11.38%)
occurrences all number	8	23
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	16 / 62 (25.81%)	47 / 123 (38.21%)
occurrences all number	18	68
Dehydration
subjects affected / exposed	5 / 62 (8.06%)	26 / 123 (21.14%)
occurrences all number	5	37
Hyperglycaemia
subjects affected / exposed	2 / 62 (3.23%)	14 / 123 (11.38%)
occurrences all number	2	22
Hypokalaemia
subjects affected / exposed	5 / 62 (8.06%)	33 / 123 (26.83%)
occurrences all number	10	49
Hyponatraemia
subjects affected / exposed	1 / 62 (1.61%)	9 / 123 (7.32%)
occurrences all number	1	11
Hypophosphataemia
subjects affected / exposed	6 / 62 (9.68%)	8 / 123 (6.50%)
occurrences all number	11	11

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

02 Feb 2018

Updated Medical Monitor and added Study Director. Revisions to laboratory tests exclusion criteria, revisions to dose modification criteria, urinalysis and biomarker sample collection requirements. Deletion of iRECIST response assessment exploratory endpoint. Addition of a definition of DILI for participants with elevated liver function tests at baseline. Updated rationale for the 2-year treatment duration, in addition of a number of other minor changes and corrections.

06 Aug 2018

Updated Medical Monitor information. Revises prohibited and/or restricted treatments; laboratory tests, assessments, and other analyses; dose modification criteria; urinalysis; and biomarker sample collection requirements. Adds additional exploratory endpoint and clarifies eligibility criteria. Updates rationale to include additional mandated biopsies. Minor changes and corrections including revisions to reflect the most recent language for BMS studies.

13 Sep 2018

Adding Appendix 11 back into the document; reinstates exclusion criteria 2j

07 Dec 2018

Clarifies the infusion days for fluorouracil, updates Appendix 3, and aligns Appendix 4 with contraceptive guidance for nivolumab and other components of study treatment.

19 Dec 2019

This revised protocol removes Interim Analysis 2 (IA2).

02 Jun 2020

Major change: Clarifies study treatment duration for standard of care (SOC). SOC may continue, after the maximum treatment duration of 24 months for nivolumab, until progression, unacceptable toxicity, withdrawal of consent, or the end of the study, whichever comes first.

13 Nov 2020

Incorporates Administrative Letter 05 and allows the last patient last visit for the progression-free survival (PFS) final analysis to be triggered when at least 114 PFS events by blinded independent central review are observed or at approximately 20 months minimum follow-up, whichever occurs first.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An Open-Label Exploratory Phase 2/3 Study of Nivolumab with Standard of Care Therapy vs Standard of Care Therapy for First-Line Treatment of Metastatic Colorectal Cancer (CheckMate 9X8: CHECKpoint pathway and nivoluMab clinical Trial Evaluation 9X8)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR)

Primary: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR)

Secondary: Objective Response Rate (ORR) per Investigator Assessment

Secondary: Objective Response Rate (ORR) per Investigator Assessment

Secondary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

Secondary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

Secondary: Progression Free Survival (PFS) per Investigator Assessment

Secondary: Progression Free Survival (PFS) per Investigator Assessment

Secondary: Time to Objective Response per Blinded Independent Central Review (BICR)

Secondary: Time to Objective Response per Blinded Independent Central Review (BICR)

Secondary: Time to Objective Response per Investigator Assessment

Secondary: Time to Objective Response per Investigator Assessment

Secondary: Duration of Response (DoR) per Blinded Independent Central Review (BICR)

Secondary: Duration of Response (DoR) per Blinded Independent Central Review (BICR)

Secondary: Number of Participants With Adverse Events (AEs)

Secondary: Number of Participants With Adverse Events (AEs)

Secondary: Duration of Response (DoR) per Investigator Assessment

Secondary: Duration of Response (DoR) per Investigator Assessment

Secondary: Number of Participants With Serious Adverse Events (SAEs)

Secondary: Number of Participants With Serious Adverse Events (SAEs)

Secondary: Disease Control Rate (DCR) per Investigator

Secondary: Disease Control Rate (DCR) per Investigator

Secondary: Disease Control Rate (DCR) per Blinded Independent Central Review (BICR)

Secondary: Disease Control Rate (DCR) per Blinded Independent Central Review (BICR)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Number of Participants Experiencing Death

Secondary: Number of Participants Experiencing Death

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Post-hoc: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR) - Extended Collection

Post-hoc: Progression Free Survival (PFS) per Blinded Independent Central Review (BICR) - Extended Collection

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An Open-Label Exploratory Phase 2/3 Study of Nivolumab with Standard of Care Therapy vs Standard of Care Therapy for First-Line Treatment of Metastatic Colorectal Cancer (CheckMate 9X8: CHECKpoint pathway and nivoluMab clinical Trial Evaluation 9X8)