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 (CheckMate 9X8)

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

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).

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0017
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0015
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0014
  • Quebec
    • Montreal, Quebec, Canada, H2X 1P1
      • Local Institution - 0048
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Local Institution - 0012
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Local Institution - 0013
    • Trois-Rivieres, Quebec, Canada, G8Z 3R9
      • Local Institution - 0016
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 4648681
      • Local Institution - 0055
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 2778577
      • Local Institution - 0051
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 4118777
      • Local Institution - 0050
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Local Institution - 0009
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0043
  • Madrid, Spain, 28034
    • Local Institution - 0042
  • Majadahonda - Madrid, Spain, 28222
    • Local Institution - 0041
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • UAB Comprehensive Cancer Center
  • California
    • Los Angeles, California, United States, 90033
      • Local Institution - 0004
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0010
    • Denver, Colorado, United States, 80218
      • Local Institution - 0027
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0020
  • Florida
    • Miami, Florida, United States, 33176
      • Local Institution - 0039
    • Saint Petersburg, Florida, United States, 33705
      • Local Institution - 0047
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Local Institution - 0033
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Local Institution - 0044
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Local Institution - 0021
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0003
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0049
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0052
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0053
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Local Institution - 0035
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0002
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • Local Institution - 0032
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Local Institution - 0029
  • New York
    • Johnson City, New York, United States, 13790
      • Local Institution - 0031
    • New York, New York, United States, 10016
      • Local Institution - 0046
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
      • Levine Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Local Institution - 0038
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0005
    • Pittsburgh, Pennsylvania, United States, 15212
      • Local Institution - 0024
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Local Institution - 0023
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Oncology & Hematology - Univ. of TN
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0019
  • Texas
    • Bedford, Texas, United States, 76022
      • Local Institution - 0026
    • Dallas, Texas, United States, 75246
      • Local Institution - 0034
    • Fort Worth, Texas, United States, 76104
      • Local Institution - 0037
    • San Antonio, Texas, United States, 78217
      • Local Institution - 0040
    • Tyler, Texas, United States, 75702
      • Local Institution - 0036
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Local Institution - 0025
    • Roanoke, Virginia, United States, 24014
      • Local Institution - 0028
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Local Institution - 0006

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per Investigator Assessment	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.	From randomization up to the date of the first documented progression (up to approximately 44 months)
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)	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.	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)
Objective Response Rate (ORR) Per Investigator Assessment	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.	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)
Duration of Response (DoR) Per Blinded Independent Central Review (BICR)	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.	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)
Duration of Response (DoR) Per Investigator Assessment	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.	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)
Time to Objective Response Per Blinded Independent Central Review (BICR)	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.	From the randomization date up to the date of the first confirmed CR or PR (up to approximately 44 months)
Time to Objective Response Per Investigator Assessment	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.	From the randomization date up to the date of the first confirmed CR or PR (up to 44 months)
Overall Survival (OS)	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.	From the date of randomization up to the date of death (up to 44 months)
Number of Participants With Adverse Events (AEs)	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.	From first dose to 30 days post last dose (up to 45 months)
Number of Participants With Serious Adverse Events (SAEs)	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.	From first dose to 30 days post last dose (up to 45 months)
Number of Participants Experiencing Death	The number of participants who died during the treatment period	From first dose up to 6 weeks post last dose (up to 46 months)
Number of Participants With Laboratory Abnormalities in Specific Liver Tests	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	From first dose up to 30 days post last dose (up to 45 months)
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests	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	From first dose up to 30 days post last dose (up to 45 months)
Disease Control Rate (DCR) Per Blinded Independent Central Review (BICR)	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.	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)
Disease Control Rate (DCR) Per Investigator	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.	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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Suibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): December 28, 2022

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Nivolumab; Bevacizumab; Leucovorin
• Other Study ID Numbers: CA209-9X8; 2017-003662-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No