CheckMate 9X8: An Investigational Immunotherapy Study of Nivolumab With Standard of Care Therapy vs Standard of Care Therapy for First-Line Treatment of Colorectal Cancer That Has Spread

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03414983
• Collaborator: Ono Pharmaceutical Co. Ltd (Industry)
• Enrollment: 195
• Locations: 49
• Arms: 2
• Anticipated Duration (Months): 64.3
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This purpose of this study is to evaluate nivolumab (BMS-936558) in combination with standard of care (SOC) chemotherapy with bevacizumab for the treatment of first-line metastatic colorectal cancer (mCRC).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Biological: Nivolumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 195 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 20, 2018
• Actual Primary Completion Date: Feb 1, 2021
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Nivo + SOC	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558 Opdivo ; Drug: Oxaliplatin; Specified dose on specified days; Drug: Leucovorin; Specified dose on specified days; Other Names: Calcium Folinate ; Drug: Fluorouracil; Specified dose on specified days; Drug: Bevacizumab; Specified dose on specified days; Other Names: Avastin
Active Comparator: Arm B SOC	Drug: Oxaliplatin; Specified dose on specified days; Drug: Leucovorin; Specified dose on specified days; Other Names: Calcium Folinate ; Drug: Fluorouracil; Specified dose on specified days; Drug: Bevacizumab; Specified dose on specified days; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR) [From randomization to up to the date of the first documented progression (up to 16 months)]

   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.

Secondary Outcome Measures

1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) [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 36 months)]

   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.

2. Objective Response Rate (ORR) Per Investigator Assessment [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 36 months)]

   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.

3. Progression Free Survival (PFS) Per Investigator Assessment [From randomization up to the date of the first documented progression (up to 16 months)]

   PFS is defined as the time from randomization to the date of the first documented progression, as determined by tumor assessments by the Investigator, or death due to any cause, whichever occurs first.

4. Time to Objective Response Per Blinded Independent Central Review (BICR) [From the randomization date up to the date of the first confirmed CR or PR (up to 36 months)]

   Time to objective response (TTR) is defined as the time from the randomization date to the date of the first confirmed CR or PR (as assessed by BICR and as assessed by investigator). TTR is derived for responders only.

5. Time to Objective Response Per Investigator Assessment [From the randomization date up to the date of the first confirmed CR or PR (up to 36 months)]

   TTR is defined as the time from the randomization date to the date of the first confirmed CR or PR (as assessed by BICR and as assessed by investigator). TTR is derived for responders only.

6. Duration of Response (DoR) Per Blinded Independent Central Review (BICR) [From the date of first confirmed response (CR or PR) up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 14 months)]

   Duration of objective response (DoR) is defined as the time between the date of first confirmed response 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.

7. Duration of Response (DoR) Per Investigator Assessment [From the date of first confirmed response (CR or PR) up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 15 months)]

   Duration of objective response (DoR) is defined as the time between the date of first confirmed response 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.

8. Overall Survival (OS) Summary [From the date of randomization up to the date of death (up to 36 months)]

   OS is defined as the time from the date of randomization to the date of death. A participant who has not died will be censored at last known date alive.

9. Number of Participants With Adverse Events (AEs) [From first dose to 30 days post last dose (up to 35 months)]

   Number of participants with any grade of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine safety and tolerability

10. Number of Participants With Serious Adverse Events (SAEs) [From first dose to 30 days post last dose (up to 35 months)]

    Number of participants with any grade of serious adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine safety and tolerability

11. Deaths [From first dose up to 6 weeks post last dose (up to 36 months)]

    The number of participants who died during the treatment period

12. Abnormalities in Specific Liver Tests [From first dose up to 30 days post last dose (up to 35 months)]

    Laboratory test results of laboratory abnormalities in hepatic parameters during the treatment period per CTCAE (Version 4) in SI units.

13. Abnormalities in Specific Thyroid Tests [From first dose up to 30 days post last dose (up to 35 months)]

    Laboratory test results of laboratory abnormalities in specific thyroid tests during the treatment period per CTCAE (Version 4) in SI units.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed metastatic colorectal cancer, not amenable to curative resection

• No prior chemotherapy for metastatic colorectal cancer

• ECOG Performance Status of 0-1

• Ability to provide adequate tissue sample

Exclusion Criteria:

• Patients with clinically relevant medical history, including autoimmune disease, cardiovascular disease, hepatic disease or bleeding disorders

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uab Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	University Of Colorado	Aurora	Colorado	United States	80045
4	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
5	Yale Cancer Center	New Haven	Connecticut	United States	06520
6	Baptist Health Medical Group	Miami	Florida	United States	33176-2118
7	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
8	Illinois Cancer Specialists	Arlington Heights	Illinois	United States	60005
9	Investigative Clinical Research Of Indiana, Llc	Indianapolis	Indiana	United States	46260
10	Regional Cancer Care Associates, LLC	Bethesda	Maryland	United States	20817
11	Beth Israel Desc. Med Ctr	Boston	Massachusetts	United States	02114
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02114
13	Mass General/North Shore Cancer Center for Outpatient Care	Boston	Massachusetts	United States	02114
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
16	Mayo Clinic	Rochester	Minnesota	United States	55905
17	Oncology Hematology West P.C. dba Nebraska Cancer Specialists	Papillion	Nebraska	United States	68046
18	Comprehensive Cancer Centers Of Nevada	Henderson	Nevada	United States	89074
19	Broome Oncology	Johnson City	New York	United States	13790
20	Laura & Isaac Perlmutter Cancer Ctr at NYU Langone	New York	New York	United States	10016
21	Levine Cancer Institute	Charlotte	North Carolina	United States	28262
22	Northwest Cancer Specialists, P.C.	Portland	Oregon	United States	97227
23	University Of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
24	Allegheny Health Network	Pittsburgh	Pennsylvania	United States	15212
25	Sanford Research	Sioux Falls	South Dakota	United States	57104
26	Erlanger Oncology & Hematology - Univ. of TN	Chattanooga	Tennessee	United States	37403
27	Tennessee Oncology, PLLC - SCRI - PPDS	Nashville	Tennessee	United States	37203
28	Texas Oncology - DFWW	Bedford	Texas	United States	76022
29	Texas Oncology-Baylor Charles A Sammons Cancer Center	Dallas	Texas	United States	75246
30	Texas Oncology-Fort Worth 12th Ave	Fort Worth	Texas	United States	76104
31	Cancer Centers of South Texas	San Antonio	Texas	United States	78217
32	Texas Oncology-Tyler	Tyler	Texas	United States	75702
33	Virginia Cancer Center	Richmond	Virginia	United States	23230
34	Oncology & Hematology Associates Of Southwest Virginia, Inc.	Roanoke	Virginia	United States	24014
35	University Of Wisconsin	Madison	Wisconsin	United States	53705
36	Cross Cancer Institute.	Edmonton	Alberta	Canada	T6G 1Z2
37	Local Institution	Ottawa	Ontario	Canada	K1H 8L6
38	Local Institution	Toronto	Ontario	Canada	M5G 2M9
39	Centre Hospitalier De L'Universite De Montreal	Montreal	Quebec	Canada	H2X 1P1
40	Centre integre universitaire de sante et de service sociaux de l'estrie - CHUS	Sherbrooke	Quebec	Canada	J1H 5N4
41	Local Institution	Trois-Rivieres	Quebec	Canada	G8Z 3R9
42	Local Institution	Quebec		Canada	G1R 2J6
43	Local Institution	Nagoya	Aichi	Japan	4648681
44	Local Institution	Kashiwa-shi	Chiba	Japan	2778577
45	Local Institution	Sunto-gun	Shizuoka	Japan	4118777
46	Fundacion De Investigacion De Diego	San Juan		Puerto Rico	00927
47	H. Univ. Vall dHebron	Barcelona		Spain	08035
48	Hospital Universitario Ramon Y Cajal	Madrid		Spain	28034
49	Hosp. Univ. Puerta De Hierro	Majadahonda - Madrid		Spain	28222

Sponsors and Collaborators

• Bristol-Myers Squibb
• Ono Pharmaceutical Co. Ltd

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Suibb

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2020
• Statistical Analysis Plan - Mar 18, 2021

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03414983
• Other Study ID Numbers: CA209-9X8; 2017-003662-27
• First Posted: Jan 30, 2018
• Last Update Posted: Mar 14, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colorectal Neoplasms; Leucovorin; Bevacizumab; Nivolumab; Fluorouracil; Oxaliplatin

Study Results

Participant Flow

Pre-assignment Detail	195 participants randomized and 185 participants treated

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Period Title: Pre-Treatment
STARTED	127	68
COMPLETED	123	62
NOT COMPLETED	4	6
Period Title: Pre-Treatment
STARTED	123	62
COMPLETED	4	2
NOT COMPLETED	119	60

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Total
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks	Total of all reporting groups
Overall Participants	127	68	195
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.8 (13.3)	57.2 (11.4)	56.9 (12.7)
Sex: Female, Male (Count of Participants)
Female	57 44.9%	19 27.9%	76 39%
Male	70 55.1%	49 72.1%	119 61%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 5.5%	9 13.2%	16 8.2%
Not Hispanic or Latino	108 85%	53 77.9%	161 82.6%
Unknown or Not Reported	12 9.4%	6 8.8%	18 9.2%
Race/Ethnicity, Customized (Number) [Number]
White	96 75.6%	57 83.8%	153 78.5%
Black or African American	8 6.3%	2 2.9%	10 5.1%
Asian	15 11.8%	5 7.4%	20 10.3%
Other	6 4.7%	3 4.4%	9 4.6%
Not Reported	2 1.6%	1 1.5%	3 1.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)
Description	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.
Time Frame	From randomization to up to the date of the first documented progression (up to 16 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	127	68
Median (95% Confidence Interval) [Months]	11.86	11.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm B
	Comments	Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3022
	Comments	Stratified regular log-rank test
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 80%; 0.61 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox proportional hazard model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm B
	Comments	Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3022
	Comments	Stratified regular log-rank test
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox proportional hazard model

2. Secondary Outcome

Title	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
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.
Time Frame	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 36 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	127	68
Number (95% Confidence Interval) [Percentage of Participants]	59.8 47.1%	45.6 67.1%

3. Secondary Outcome

Title	Objective Response Rate (ORR) Per Investigator Assessment
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.
Time Frame	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 36 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	127	68
Number (95% Confidence Interval) [Percentage of participants]	61.4 48.3%	51.5 75.7%

4. Secondary Outcome

Title	Progression Free Survival (PFS) Per Investigator Assessment
Description	PFS is defined as the time from randomization to the date of the first documented progression, as determined by tumor assessments by the Investigator, or death due to any cause, whichever occurs first.
Time Frame	From randomization up to the date of the first documented progression (up to 16 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	127	68
Median (95% Confidence Interval) [Months]	13.24	12.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm B
	Comments	Hazard Ratio is Arm A: NIV+mFOLFOX+BEV over Arm B: mFOLFOX+BEV
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox proportional hazard model

5. Secondary Outcome

Title	Time to Objective Response Per Blinded Independent Central Review (BICR)
Description	Time to objective response (TTR) is defined as the time from the randomization date to the date of the first confirmed CR or PR (as assessed by BICR and as assessed by investigator). TTR is derived for responders only.
Time Frame	From the randomization date up to the date of the first confirmed CR or PR (up to 36 months)

Outcome Measure Data

Analysis Population Description

All Responders

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	76	31
Median (Standard Deviation) [Months]	2.81 (1.61)	2.83 (1.45)

6. Secondary Outcome

Title	Time to Objective Response Per Investigator Assessment
Description	TTR is defined as the time from the randomization date to the date of the first confirmed CR or PR (as assessed by BICR and as assessed by investigator). TTR is derived for responders only.
Time Frame	From the randomization date up to the date of the first confirmed CR or PR (up to 36 months)

Outcome Measure Data

Analysis Population Description

All Responders

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	78	35
Median (Standard Deviation) [Months]	2.83 (2.15)	2.83 (1.45)

7. Secondary Outcome

Title	Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
Description	Duration of objective response (DoR) is defined as the time between the date of first confirmed response 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.
Time Frame	From the date of first confirmed response (CR or PR) up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 14 months)

Outcome Measure Data

Analysis Population Description

All Responders

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	76	31
Median (95% Confidence Interval) [Months]	12.88	9.26

8. Secondary Outcome

Title	Duration of Response (DoR) Per Investigator Assessment
Description	Duration of objective response (DoR) is defined as the time between the date of first confirmed response 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.
Time Frame	From the date of first confirmed response (CR or PR) up to the date of the first documented progression (per RECIST 1.1) or death due to any cause, whichever occurs first (up to 15 months)

Outcome Measure Data

Analysis Population Description

All Responders

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	78	35
Median (95% Confidence Interval) [Months]	11.89	10.84

9. Secondary Outcome

Title	Overall Survival (OS) Summary
Description	OS is defined as the time from the date of randomization to the date of death. A participant who has not died will be censored at last known date alive.
Time Frame	From the date of randomization up to the date of death (up to 36 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	127	68
Median (95% Confidence Interval) [Months]	29.24	NA

10. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	Number of participants with any grade of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine safety and tolerability
Time Frame	From first dose to 30 days post last dose (up to 35 months)

Outcome Measure Data

Analysis Population Description

All participants who have received at least 1 dose of study treatment

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	123	62
Count of Participants [Participants]	122 96.1%	61 89.7%

11. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	Number of participants with any grade of serious adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine safety and tolerability
Time Frame	From first dose to 30 days post last dose (up to 35 months)

Outcome Measure Data

Analysis Population Description

All participants who have received at least 1 dose of study treatment

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	123	62
Count of Participants [Participants]	56 44.1%	20 29.4%

12. Secondary Outcome

Title	Deaths
Description	The number of participants who died during the treatment period
Time Frame	From first dose up to 6 weeks post last dose (up to 36 months)

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	123	62
Count of Participants [Participants]	53 41.7%	24 35.3%

13. Secondary Outcome

Title	Abnormalities in Specific Liver Tests
Description	Laboratory test results of laboratory abnormalities in hepatic parameters during the treatment period per CTCAE (Version 4) in SI units.
Time Frame	From first dose up to 30 days post last dose (up to 35 months)

Outcome Measure Data

Analysis Population Description

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	123	61
ALT OR AST > 3XULN	16 12.6%	6 8.8%
ALT OR AST > 5XULN	7 5.5%	2 2.9%
ALT OR AST > 10XULN	2 1.6%	0 0%
ALT OR AST > 20XULN	0 0%	0 0%
TOTAL BILIRUBIN > 2XULN	0 0%	1 1.5%
ALP > 1.5XULN	38 29.9%	20 29.4%
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY	2 1.6%	1 1.5%
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS	2 1.6%	1 1.5%
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY	0 0%	1 1.5%
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS	0 0%	1 1.5%

14. Secondary Outcome

Title	Abnormalities in Specific Thyroid Tests
Description	Laboratory test results of laboratory abnormalities in specific thyroid tests during the treatment period per CTCAE (Version 4) in SI units.
Time Frame	From first dose up to 30 days post last dose (up to 35 months)

Outcome Measure Data

Analysis Population Description

All Treated Participants with at Least One On-Treatment TSH measurement

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks	mFOLFOX6/bevacizumab (SOC) every 2 weeks
Measure Participants	123	60
TSH > ULN	45 35.4%	23 33.8%
TSH > ULN WITH TSH <= ULN AT BASELINE	37 29.1%	16 23.5%
TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN	20 15.7%	2 2.9%
TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN	11 8.7%	9 13.2%
TSH > ULN WITH FT3/FT4 TEST MISSING	14 11%	12 17.6%
TSH < LLN	25 19.7%	3 4.4%
TSH < LLN WITH TSH >= LLN AT BASELINE	22 17.3%	3 4.4%
TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN	13 10.2%	0 0%
TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	8 6.3%	2 2.9%
TSH < LLN WITH FT3/FT4 TEST MISSING	4 3.1%	1 1.5%

Adverse Events

Time Frame	From first dose to 100 days post last dose (Up to 37 months)
Arm/Group Title	Arm A		Arm B
Arm/Group Description	Nivolumab 240 mg + Standard of Care (SOC) mFOLFOX6/bevacizuma every 2 weeks		mFOLFOX6/bevacizumab (SOC) every 2 weeks
All Cause Mortality
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/123 (43.1%)		24/62 (38.7%)
Serious Adverse Events
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/123 (52.8%)		25/62 (40.3%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/123 (0.8%)		0/62 (0%)
Febrile neutropenia	6/123 (4.9%)		1/62 (1.6%)
Cardiac disorders
Cardiac arrest	1/123 (0.8%)		1/62 (1.6%)
Intracardiac thrombus	1/123 (0.8%)		0/62 (0%)
Myocardial infarction	1/123 (0.8%)		0/62 (0%)
Myocarditis	1/123 (0.8%)		0/62 (0%)
Tachycardia	1/123 (0.8%)		0/62 (0%)
Gastrointestinal disorders
Abdominal pain	5/123 (4.1%)		3/62 (4.8%)
Abdominal pain upper	0/123 (0%)		1/62 (1.6%)
Ascites	1/123 (0.8%)		0/62 (0%)
Colitis	9/123 (7.3%)		0/62 (0%)
Constipation	1/123 (0.8%)		1/62 (1.6%)
Diarrhoea	3/123 (2.4%)		0/62 (0%)
Duodenal ulcer	1/123 (0.8%)		0/62 (0%)
Gastritis	1/123 (0.8%)		0/62 (0%)
Ileus	1/123 (0.8%)		0/62 (0%)
Immune-mediated enterocolitis	1/123 (0.8%)		0/62 (0%)
Intestinal obstruction	3/123 (2.4%)		1/62 (1.6%)
Intestinal perforation	1/123 (0.8%)		2/62 (3.2%)
Large intestinal obstruction	2/123 (1.6%)		1/62 (1.6%)
Large intestine perforation	1/123 (0.8%)		0/62 (0%)
Lower gastrointestinal haemorrhage	1/123 (0.8%)		0/62 (0%)
Mesenteric vein thrombosis	0/123 (0%)		1/62 (1.6%)
Nausea	3/123 (2.4%)		0/62 (0%)
Pancreatitis	1/123 (0.8%)		0/62 (0%)
Pancreatitis acute	2/123 (1.6%)		0/62 (0%)
Proctalgia	1/123 (0.8%)		1/62 (1.6%)
Rectal haemorrhage	1/123 (0.8%)		0/62 (0%)
Rectal perforation	1/123 (0.8%)		0/62 (0%)
Small intestinal obstruction	3/123 (2.4%)		0/62 (0%)
Upper gastrointestinal haemorrhage	1/123 (0.8%)		0/62 (0%)
Vomiting	3/123 (2.4%)		0/62 (0%)
General disorders
Asthenia	1/123 (0.8%)		0/62 (0%)
Death	2/123 (1.6%)		2/62 (3.2%)
Infusion site extravasation	1/123 (0.8%)		0/62 (0%)
Non-cardiac chest pain	1/123 (0.8%)		1/62 (1.6%)
Pain	1/123 (0.8%)		0/62 (0%)
Pyrexia	3/123 (2.4%)		1/62 (1.6%)
Hepatobiliary disorders
Autoimmune hepatitis	1/123 (0.8%)		0/62 (0%)
Cholangitis	1/123 (0.8%)		0/62 (0%)
Hepatic lesion	1/123 (0.8%)		0/62 (0%)
Infections and infestations
Abdominal abscess	1/123 (0.8%)		1/62 (1.6%)
Abdominal infection	0/123 (0%)		1/62 (1.6%)
Abscess neck	1/123 (0.8%)		0/62 (0%)
Clostridium difficile infection	1/123 (0.8%)		1/62 (1.6%)
Diarrhoea infectious	1/123 (0.8%)		0/62 (0%)
Diverticulitis	1/123 (0.8%)		0/62 (0%)
Endocarditis bacterial	1/123 (0.8%)		0/62 (0%)
Gastroenteritis	0/123 (0%)		1/62 (1.6%)
Gastroenteritis norovirus	1/123 (0.8%)		0/62 (0%)
Influenza	0/123 (0%)		1/62 (1.6%)
Oesophageal candidiasis	1/123 (0.8%)		0/62 (0%)
Perirectal abscess	0/123 (0%)		1/62 (1.6%)
Peritonitis bacterial	1/123 (0.8%)		0/62 (0%)
Pneumonia	4/123 (3.3%)		0/62 (0%)
Pneumonia pseudomonal	1/123 (0.8%)		0/62 (0%)
Rectal abscess	1/123 (0.8%)		0/62 (0%)
Sepsis	6/123 (4.9%)		1/62 (1.6%)
Vascular device infection	1/123 (0.8%)		0/62 (0%)
Viral upper respiratory tract infection	0/123 (0%)		1/62 (1.6%)
Injury, poisoning and procedural complications
Fall	0/123 (0%)		1/62 (1.6%)
Forearm fracture	0/123 (0%)		1/62 (1.6%)
Gastrointestinal anastomotic leak	1/123 (0.8%)		0/62 (0%)
Incisional hernia	0/123 (0%)		1/62 (1.6%)
Thoracic vertebral fracture	1/123 (0.8%)		0/62 (0%)
Investigations
Aspartate aminotransferase increased	1/123 (0.8%)		0/62 (0%)
Blood bilirubin increased	0/123 (0%)		1/62 (1.6%)
Blood potassium increased	1/123 (0.8%)		0/62 (0%)
Neutrophil count decreased	1/123 (0.8%)		1/62 (1.6%)
Platelet count decreased	1/123 (0.8%)		0/62 (0%)
Metabolism and nutrition disorders
Dehydration	1/123 (0.8%)		0/62 (0%)
Diabetic ketoacidosis	1/123 (0.8%)		0/62 (0%)
Failure to thrive	2/123 (1.6%)		0/62 (0%)
Hyponatraemia	1/123 (0.8%)		0/62 (0%)
Metabolic acidosis	1/123 (0.8%)		0/62 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/123 (0.8%)		0/62 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	0/123 (0%)		1/62 (1.6%)
Malignant neoplasm progression	6/123 (4.9%)		1/62 (1.6%)
Metastases to liver	0/123 (0%)		1/62 (1.6%)
Metastases to ovary	1/123 (0.8%)		0/62 (0%)
Nervous system disorders
Depressed level of consciousness	0/123 (0%)		1/62 (1.6%)
Syncope	1/123 (0.8%)		0/62 (0%)
Psychiatric disorders
Depression	1/123 (0.8%)		1/62 (1.6%)
Renal and urinary disorders
Acute kidney injury	1/123 (0.8%)		0/62 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/123 (0.8%)		0/62 (0%)
Chronic obstructive pulmonary disease	1/123 (0.8%)		0/62 (0%)
Dyspnoea	0/123 (0%)		1/62 (1.6%)
Pleural effusion	1/123 (0.8%)		0/62 (0%)
Pneumonitis	2/123 (1.6%)		0/62 (0%)
Pneumothorax	1/123 (0.8%)		0/62 (0%)
Pulmonary embolism	6/123 (4.9%)		2/62 (3.2%)
Pulmonary oedema	0/123 (0%)		1/62 (1.6%)
Vascular disorders
Deep vein thrombosis	0/123 (0%)		1/62 (1.6%)
Embolism	1/123 (0.8%)		0/62 (0%)
Hypotension	1/123 (0.8%)		0/62 (0%)
Orthostatic hypotension	1/123 (0.8%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	122/123 (99.2%)		61/62 (98.4%)
Blood and lymphatic system disorders
Anaemia	30/123 (24.4%)		12/62 (19.4%)
Neutropenia	45/123 (36.6%)		14/62 (22.6%)
Thrombocytopenia	26/123 (21.1%)		7/62 (11.3%)
Cardiac disorders
Tachycardia	7/123 (5.7%)		1/62 (1.6%)
Endocrine disorders
Hyperthyroidism	7/123 (5.7%)		1/62 (1.6%)
Hypothyroidism	22/123 (17.9%)		1/62 (1.6%)
Gastrointestinal disorders
Abdominal distension	7/123 (5.7%)		2/62 (3.2%)
Abdominal pain	39/123 (31.7%)		19/62 (30.6%)
Abdominal pain upper	12/123 (9.8%)		3/62 (4.8%)
Colitis	7/123 (5.7%)		1/62 (1.6%)
Constipation	52/123 (42.3%)		21/62 (33.9%)
Diarrhoea	74/123 (60.2%)		20/62 (32.3%)
Dry mouth	15/123 (12.2%)		3/62 (4.8%)
Dyspepsia	15/123 (12.2%)		6/62 (9.7%)
Gastrooesophageal reflux disease	7/123 (5.7%)		5/62 (8.1%)
Haemorrhoids	6/123 (4.9%)		4/62 (6.5%)
Nausea	82/123 (66.7%)		35/62 (56.5%)
Proctalgia	11/123 (8.9%)		2/62 (3.2%)
Stomatitis	28/123 (22.8%)		18/62 (29%)
Toothache	5/123 (4.1%)		4/62 (6.5%)
Vomiting	47/123 (38.2%)		13/62 (21%)
General disorders
Asthenia	22/123 (17.9%)		6/62 (9.7%)
Chills	17/123 (13.8%)		1/62 (1.6%)
Fatigue	73/123 (59.3%)		38/62 (61.3%)
Influenza like illness	10/123 (8.1%)		1/62 (1.6%)
Malaise	7/123 (5.7%)		3/62 (4.8%)
Mucosal inflammation	14/123 (11.4%)		12/62 (19.4%)
Non-cardiac chest pain	5/123 (4.1%)		4/62 (6.5%)
Oedema peripheral	12/123 (9.8%)		2/62 (3.2%)
Pain	9/123 (7.3%)		3/62 (4.8%)
Pyrexia	33/123 (26.8%)		10/62 (16.1%)
Temperature intolerance	32/123 (26%)		13/62 (21%)
Immune system disorders
Hypersensitivity	10/123 (8.1%)		2/62 (3.2%)
Infections and infestations
Upper respiratory tract infection	17/123 (13.8%)		5/62 (8.1%)
Urinary tract infection	14/123 (11.4%)		7/62 (11.3%)
Injury, poisoning and procedural complications
Fall	11/123 (8.9%)		1/62 (1.6%)
Infusion related reaction	27/123 (22%)		5/62 (8.1%)
Investigations
Alanine aminotransferase increased	16/123 (13%)		7/62 (11.3%)
Aspartate aminotransferase increased	22/123 (17.9%)		6/62 (9.7%)
Blood alkaline phosphatase increased	15/123 (12.2%)		4/62 (6.5%)
Blood creatinine increased	11/123 (8.9%)		2/62 (3.2%)
Neutrophil count decreased	38/123 (30.9%)		12/62 (19.4%)
Platelet count decreased	25/123 (20.3%)		10/62 (16.1%)
Weight decreased	18/123 (14.6%)		12/62 (19.4%)
White blood cell count decreased	15/123 (12.2%)		5/62 (8.1%)
Metabolism and nutrition disorders
Decreased appetite	47/123 (38.2%)		16/62 (25.8%)
Dehydration	26/123 (21.1%)		5/62 (8.1%)
Hyperglycaemia	14/123 (11.4%)		2/62 (3.2%)
Hypokalaemia	32/123 (26%)		5/62 (8.1%)
Hyponatraemia	8/123 (6.5%)		1/62 (1.6%)
Hypophosphataemia	8/123 (6.5%)		6/62 (9.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	38/123 (30.9%)		9/62 (14.5%)
Back pain	24/123 (19.5%)		9/62 (14.5%)
Bone pain	5/123 (4.1%)		4/62 (6.5%)
Muscle spasms	10/123 (8.1%)		0/62 (0%)
Muscular weakness	11/123 (8.9%)		3/62 (4.8%)
Myalgia	10/123 (8.1%)		3/62 (4.8%)
Pain in extremity	20/123 (16.3%)		3/62 (4.8%)
Nervous system disorders
Dizziness	22/123 (17.9%)		9/62 (14.5%)
Dysgeusia	25/123 (20.3%)		12/62 (19.4%)
Headache	25/123 (20.3%)		5/62 (8.1%)
Hypoaesthesia	4/123 (3.3%)		6/62 (9.7%)
Neuropathy peripheral	53/123 (43.1%)		21/62 (33.9%)
Neurotoxicity	12/123 (9.8%)		2/62 (3.2%)
Paraesthesia	11/123 (8.9%)		5/62 (8.1%)
Peripheral sensory neuropathy	44/123 (35.8%)		28/62 (45.2%)
Taste disorder	8/123 (6.5%)		2/62 (3.2%)
Psychiatric disorders
Anxiety	13/123 (10.6%)		1/62 (1.6%)
Depression	13/123 (10.6%)		3/62 (4.8%)
Insomnia	31/123 (25.2%)		10/62 (16.1%)
Renal and urinary disorders
Proteinuria	17/123 (13.8%)		9/62 (14.5%)
Respiratory, thoracic and mediastinal disorders
Cough	28/123 (22.8%)		10/62 (16.1%)
Dysphonia	16/123 (13%)		6/62 (9.7%)
Dyspnoea	26/123 (21.1%)		3/62 (4.8%)
Epistaxis	39/123 (31.7%)		13/62 (21%)
Hiccups	5/123 (4.1%)		6/62 (9.7%)
Nasal congestion	7/123 (5.7%)		3/62 (4.8%)
Oropharyngeal pain	6/123 (4.9%)		4/62 (6.5%)
Rhinorrhoea	9/123 (7.3%)		5/62 (8.1%)
Skin and subcutaneous tissue disorders
Alopecia	9/123 (7.3%)		6/62 (9.7%)
Dry skin	17/123 (13.8%)		6/62 (9.7%)
Palmar-plantar erythrodysaesthesia syndrome	14/123 (11.4%)		8/62 (12.9%)
Pruritus	12/123 (9.8%)		2/62 (3.2%)
Rash	14/123 (11.4%)		5/62 (8.1%)
Rash maculo-papular	11/123 (8.9%)		0/62 (0%)
Skin hyperpigmentation	9/123 (7.3%)		3/62 (4.8%)
Vascular disorders
Hypertension	38/123 (30.9%)		12/62 (19.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.