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CheckMate 812: A Study of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Patients With Advanced Stage Classical Hodgkin Lymphoma, Who Are Relapsed/ Refractory or Who Are Not Eligible for Autologous Stem Cell Transplant,

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT03138499
Collaborator
Seagen Inc. (Industry), Ono Pharmaceutical Co. Ltd (Industry)
23
Enrollment
22
Locations
2
Arms
43.9
Actual Duration (Months)
1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether an investigational immuno-therapy combination, nivolumab with Brentuximab vedotin compared to Brentuximab vedotin alone is safe and effective in the treatment of relapsed and refractory Classical Hodgkin Lymphoma. The participants of this trial will comprise of patients who have relapsed or did not respond to treatment and are not eligible for stem cell transplant

Condition or Disease Intervention/Treatment Phase
  • Biological: Nivolumab
  • Biological: Brentuximab vedotin
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized, Open-label, Phase 3 Trial of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Participants With Relapsed Refractory or Ineligible for Autologous Stem Cell Transplant (ASCT) Advanced Stage Classical Hodgkin Lymphoma (CheckMate 812: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 812)
Actual Study Start Date :
Jun 26, 2017
Actual Primary Completion Date :
Feb 22, 2021
Actual Study Completion Date :
Feb 22, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Module A

Nivolumab combined with Brentuximab

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo

    • Biological: Brentuximab vedotin
    Specified dose on specified days
    Other Names:
  • Adcetris

    		•
    Experimental: Module B

    Brentuximab alone

    Biological: Brentuximab vedotin
    Specified dose on specified days
    Other Names:
  • Adcetris

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [From randomization to date of death, or disease progression (up to approximately 45 months)]

      Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method.

    Secondary Outcome Measures

    1. Complete Response Rate (CRR): [From randomization up to approximately 45 months]

      Complete Response Rate (CRR) is defined as the number of participants who have achieved complete response (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).

    2. Objective Response Rate (ORR) [From randomization up to approximately 45 months]

      Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).

    3. Duration of Response (DOR) [From randomization to date of documented progression or death (up to approximately 45 months)]

      The time from first response (Complete response (CR) or partial response (PR)) to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).

    4. Duration of Complete Response (DOCR) [From randomization to date of documented progression or death (up to approximately 45 months)]

      Duration of complete response (DOR) is defined as the time from first complete response to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).

    5. Overall Survival (OS) [From randomization to the date of death (up to approximately 3 years 7 months)]

      Overall Survival (OS) is defined as the time between the date of randomization and the date of death estimated using the Kaplan-Meier (KM) product-limit method

    Eligibility Criteria

    Criteria

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

    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

    • Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following:

    1. Autologous stem cell transplant (ASCT) ineligible patients
    1. Patients after failure of ASCT
    • Must have at least one lesion that is > 15 mm (1.5 cm) in the longest diameter and avid by Fluoro Deoxy Glucose (FDG) Positron Emission Tomography (PET) scan
    Exclusion Criteria:

    • Known central nervous system lymphoma

    • Participants with nodular lymphocyte-predominant Hodgkin lymphoma (HL)

    • Participants with known history of pancreatitis or progressive multifocal leukoencephalopathy (PML)

    Other protocol-defined inclusion/exclusion criteria apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 Pacific Shores Medical Group Long Beach California United States 90813
    3 University of Southern California Los Angeles California United States 90033
    4 UCLA Clinical and Translational Research Center (CTRC) Los Angeles California United States 90095
    5 Local Institution Palo Alto California United States 94304
    6 UC Davis Comprehensive Cancer Center Sacramento California United States 95817
    7 University of California San Diego San Diego California United States 92122
    8 Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut Plainville Connecticut United States 06062
    9 Orlando Health, Inc Orlando Florida United States 32806
    10 Parkview Cancer Center Fort Wayne Indiana United States 46845
    11 University of Kansas Cancer Center Westwood Kansas United States 66205
    12 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    13 Dana Farber/Harvard Cancer Center Boston Massachusetts United States 02215
    14 Karmanos Cancer Institute Detroit Michigan United States 48201
    15 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    16 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    17 Bon Secours Saint Francis Cancer Center Greenville South Carolina United States 29607
    18 Vanderbilt Ingram Cancer Center Nashville Tennessee United States 37213
    19 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    20 The University of Texas MD Anderson Cancer Center-merge Houston Texas United States 77030
    21 Local Institution Sendai-shi Miyagi Japan 9808574
    22 Local Institution San Juan Puerto Rico 00918

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Seagen Inc.
    • Ono Pharmaceutical Co. Ltd

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT03138499
    Other Study ID Numbers:
    • CA209-812
    • 2017-000847-41
    First Posted:
    May 3, 2017
    Last Update Posted:
    Apr 12, 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:
    Hodgkin Disease
    Nivolumab
    Brentuximab Vedotin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 23 participants were randomized for study participation, 22 received at least 1 dose of study drug.
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity, whichever occurs first
    Period Title: Overall Study
    STARTED 12 11
    COMPLETED 3 1
    NOT COMPLETED 9 10

    Baseline Characteristics

    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV) Total
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity, whichever occurs first Total of all reporting groups
    Overall Participants 12 11 23
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    37.5
    (13.1)
    42.3
    (16.1)
    39.8
    (14.5)
    Sex: Female, Male (Count of Participants)
    Female
    5
    41.7%
    3
    27.3%
    8
    34.8%
    Male
    7
    58.3%
    8
    72.7%
    15
    65.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    16.7%
    3
    27.3%
    5
    21.7%
    Not Hispanic or Latino
    9
    75%
    7
    63.6%
    16
    69.6%
    Unknown or Not Reported
    1
    8.3%
    1
    9.1%
    2
    8.7%
    Race/Ethnicity, Customized (Count of Participants)
    WHITE
    7
    58.3%
    4
    36.4%
    11
    47.8%
    BLACK OR AFRICAN AMERICAN
    3
    25%
    2
    18.2%
    5
    21.7%
    JAPANESE
    0
    0%
    1
    9.1%
    1
    4.3%
    ASIAN OTHER
    0
    0%
    1
    9.1%
    1
    4.3%
    NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
    1
    8.3%
    0
    0%
    1
    4.3%
    OTHER
    1
    8.3%
    3
    27.3%
    4
    17.4%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS)
    Description Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method.
    Time Frame From randomization to date of death, or disease progression (up to approximately 45 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity, whichever occurs first
    Measure Participants 12 11
    Median (95% Confidence Interval) [Months]
    14.32
    7.93
    2. Secondary Outcome
    Title Complete Response Rate (CRR):
    Description Complete Response Rate (CRR) is defined as the number of participants who have achieved complete response (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
    Time Frame From randomization up to approximately 45 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for 16 cycles, or until progression or unacceptable toxicity, whichever occurs first
    Measure Participants 12 11
    Count of Participants [Participants]
    4
    33.3%
    3
    27.3%
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
    Time Frame From randomization up to approximately 45 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for 16 cycles, or until progression or unacceptable toxicity, whichever occurs first
    Measure Participants 12 11
    Count of Participants [Participants]
    8
    66.7%
    5
    45.5%
    4. Secondary Outcome
    Title Duration of Response (DOR)
    Description The time from first response (Complete response (CR) or partial response (PR)) to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
    Time Frame From randomization to date of documented progression or death (up to approximately 45 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for 16 cycles, or until progression or unacceptable toxicity, whichever occurs first
    Measure Participants 8 5
    Median (95% Confidence Interval) [Months]
    11.27
    7.00
    5. Secondary Outcome
    Title Duration of Complete Response (DOCR)
    Description Duration of complete response (DOR) is defined as the time from first complete response to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
    Time Frame From randomization to date of documented progression or death (up to approximately 45 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with objective response of complete response (CR)
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for 16 cycles, or until progression or unacceptable toxicity, whichever occurs first
    Measure Participants 4 3
    Median (95% Confidence Interval) [Months]
    7.85
    NA
    6. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall Survival (OS) is defined as the time between the date of randomization and the date of death estimated using the Kaplan-Meier (KM) product-limit method
    Time Frame From randomization to the date of death (up to approximately 3 years 7 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for 16 cycles, or until progression or unacceptable toxicity, whichever occurs first
    Measure Participants 12 11
    Median (95% Confidence Interval) [Months]
    NA
    NA

    Adverse Events

    Time Frame From first dose to up to 100 days post last dose (up to approximately 2 years) All-cause mortality was assessed from date of first dose to study completion (up to approximately 3 years 7 months)
    Adverse Event Reporting Description 23 participants were randomized for study participation, 22 received at least 1 dose of study drug and one participant discontinued study before treatment. Adverse events were collected for all treated participants who received at least 1 dose of study treatment.
    Arm/Group Title Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Arm/Group Description Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. BV alone 1.8 mg/kg every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity, whichever occurs first
    All Cause Mortality
    Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/12 (8.3%) 0/10 (0%)
    Serious Adverse Events
    Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/12 (50%) 1/10 (10%)
    General disorders
    Non-cardiac chest pain 0/12 (0%) 1/10 (10%)
    Pyrexia 1/12 (8.3%) 0/10 (0%)
    Infections and infestations
    Adenovirus infection 1/12 (8.3%) 0/10 (0%)
    Herpes zoster 1/12 (8.3%) 0/10 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 2/12 (16.7%) 0/10 (0%)
    Nervous system disorders
    Seizure 1/12 (8.3%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 1/12 (8.3%) 0/10 (0%)
    Pulmonary embolism 1/12 (8.3%) 0/10 (0%)
    Skin and subcutaneous tissue disorders
    Rash 1/12 (8.3%) 0/10 (0%)
    Vascular disorders
    Embolism 0/12 (0%) 1/10 (10%)
    Other (Not Including Serious) Adverse Events
    Nivolumab + Brentuximab Vedotin (BV) Brentuximab Vedotin (BV)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/12 (100%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia 2/12 (16.7%) 2/10 (20%)
    Leukopenia 1/12 (8.3%) 2/10 (20%)
    Lymph node pain 1/12 (8.3%) 0/10 (0%)
    Neutropenia 1/12 (8.3%) 3/10 (30%)
    Pancytopenia 1/12 (8.3%) 0/10 (0%)
    Cardiac disorders
    Bradycardia 1/12 (8.3%) 0/10 (0%)
    Palpitations 1/12 (8.3%) 0/10 (0%)
    Tachycardia 2/12 (16.7%) 0/10 (0%)
    Ear and labyrinth disorders
    Ear pain 0/12 (0%) 1/10 (10%)
    Vertigo 0/12 (0%) 1/10 (10%)
    Eye disorders
    Eye discharge 1/12 (8.3%) 0/10 (0%)
    Eye pruritus 1/12 (8.3%) 0/10 (0%)
    Scleral hyperaemia 1/12 (8.3%) 0/10 (0%)
    Vision blurred 1/12 (8.3%) 0/10 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/12 (0%) 1/10 (10%)
    Abdominal distension 1/12 (8.3%) 0/10 (0%)
    Abdominal pain lower 1/12 (8.3%) 0/10 (0%)
    Abdominal pain upper 1/12 (8.3%) 0/10 (0%)
    Constipation 5/12 (41.7%) 1/10 (10%)
    Diarrhoea 1/12 (8.3%) 0/10 (0%)
    Dry mouth 1/12 (8.3%) 0/10 (0%)
    Dyspepsia 1/12 (8.3%) 1/10 (10%)
    Gastrooesophageal reflux disease 1/12 (8.3%) 2/10 (20%)
    Haemorrhoids 0/12 (0%) 1/10 (10%)
    Mouth ulceration 0/12 (0%) 1/10 (10%)
    Nausea 4/12 (33.3%) 4/10 (40%)
    Vomiting 3/12 (25%) 0/10 (0%)
    General disorders
    Chest pain 2/12 (16.7%) 0/10 (0%)
    Chills 3/12 (25%) 0/10 (0%)
    Fatigue 6/12 (50%) 4/10 (40%)
    Influenza like illness 0/12 (0%) 1/10 (10%)
    Malaise 0/12 (0%) 1/10 (10%)
    Mucosal inflammation 1/12 (8.3%) 0/10 (0%)
    Non-cardiac chest pain 4/12 (33.3%) 0/10 (0%)
    Pain 1/12 (8.3%) 0/10 (0%)
    Pyrexia 4/12 (33.3%) 2/10 (20%)
    Infections and infestations
    Abscess jaw 1/12 (8.3%) 0/10 (0%)
    Body tinea 0/12 (0%) 1/10 (10%)
    Cystitis 1/12 (8.3%) 0/10 (0%)
    Fungal skin infection 1/12 (8.3%) 0/10 (0%)
    Herpes zoster 2/12 (16.7%) 0/10 (0%)
    Nasopharyngitis 0/12 (0%) 1/10 (10%)
    Oral infection 1/12 (8.3%) 0/10 (0%)
    Rhinitis 1/12 (8.3%) 0/10 (0%)
    Scrotal abscess 1/12 (8.3%) 0/10 (0%)
    Sinusitis 1/12 (8.3%) 0/10 (0%)
    Upper respiratory tract infection 2/12 (16.7%) 0/10 (0%)
    Urinary tract infection 1/12 (8.3%) 0/10 (0%)
    Viral infection 0/12 (0%) 1/10 (10%)
    Viral pericarditis 1/12 (8.3%) 0/10 (0%)
    Injury, poisoning and procedural complications
    Fall 2/12 (16.7%) 1/10 (10%)
    Hip fracture 0/12 (0%) 1/10 (10%)
    Infusion related reaction 1/12 (8.3%) 1/10 (10%)
    Ligament sprain 0/12 (0%) 1/10 (10%)
    Limb injury 1/12 (8.3%) 0/10 (0%)
    Investigations
    Alanine aminotransferase increased 2/12 (16.7%) 2/10 (20%)
    Aspartate aminotransferase increased 2/12 (16.7%) 3/10 (30%)
    Blood alkaline phosphatase increased 1/12 (8.3%) 2/10 (20%)
    Blood bilirubin decreased 0/12 (0%) 1/10 (10%)
    Blood bilirubin increased 0/12 (0%) 1/10 (10%)
    Blood thyroid stimulating hormone increased 1/12 (8.3%) 0/10 (0%)
    Blood uric acid increased 1/12 (8.3%) 0/10 (0%)
    Breath sounds abnormal 1/12 (8.3%) 0/10 (0%)
    Ejection fraction decreased 1/12 (8.3%) 0/10 (0%)
    Gamma-glutamyltransferase increased 0/12 (0%) 1/10 (10%)
    Hepatic enzyme increased 0/12 (0%) 1/10 (10%)
    Influenza B virus test positive 1/12 (8.3%) 0/10 (0%)
    Lymphocyte count decreased 1/12 (8.3%) 2/10 (20%)
    Neutrophil count decreased 2/12 (16.7%) 2/10 (20%)
    Platelet count decreased 1/12 (8.3%) 1/10 (10%)
    Weight decreased 2/12 (16.7%) 1/10 (10%)
    Weight increased 1/12 (8.3%) 0/10 (0%)
    White blood cell count decreased 2/12 (16.7%) 2/10 (20%)
    Metabolism and nutrition disorders
    Decreased appetite 2/12 (16.7%) 0/10 (0%)
    Diabetes mellitus 0/12 (0%) 1/10 (10%)
    Hyperglycaemia 1/12 (8.3%) 1/10 (10%)
    Hypokalaemia 2/12 (16.7%) 1/10 (10%)
    Hypomagnesaemia 3/12 (25%) 2/10 (20%)
    Hypophosphataemia 2/12 (16.7%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/12 (16.7%) 1/10 (10%)
    Back pain 0/12 (0%) 1/10 (10%)
    Bone pain 2/12 (16.7%) 0/10 (0%)
    Musculoskeletal chest pain 2/12 (16.7%) 0/10 (0%)
    Myalgia 1/12 (8.3%) 0/10 (0%)
    Pain in extremity 0/12 (0%) 2/10 (20%)
    Nervous system disorders
    Dizziness 2/12 (16.7%) 1/10 (10%)
    Dysgeusia 1/12 (8.3%) 0/10 (0%)
    Headache 6/12 (50%) 2/10 (20%)
    Neuropathy peripheral 6/12 (50%) 6/10 (60%)
    Peripheral sensory neuropathy 4/12 (33.3%) 1/10 (10%)
    Psychiatric disorders
    Anxiety 3/12 (25%) 1/10 (10%)
    Depression 1/12 (8.3%) 0/10 (0%)
    Insomnia 3/12 (25%) 0/10 (0%)
    Renal and urinary disorders
    Urinary incontinence 0/12 (0%) 1/10 (10%)
    Urine odour abnormal 1/12 (8.3%) 0/10 (0%)
    Reproductive system and breast disorders
    Sexual dysfunction 0/12 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/12 (41.7%) 2/10 (20%)
    Dyspnoea 2/12 (16.7%) 1/10 (10%)
    Haemoptysis 1/12 (8.3%) 0/10 (0%)
    Laryngeal inflammation 1/12 (8.3%) 0/10 (0%)
    Nasal congestion 1/12 (8.3%) 0/10 (0%)
    Oropharyngeal pain 4/12 (33.3%) 1/10 (10%)
    Pneumonitis 1/12 (8.3%) 0/10 (0%)
    Productive cough 1/12 (8.3%) 0/10 (0%)
    Respiratory tract congestion 0/12 (0%) 1/10 (10%)
    Rhinorrhoea 1/12 (8.3%) 0/10 (0%)
    Upper-airway cough syndrome 1/12 (8.3%) 0/10 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis 1/12 (8.3%) 0/10 (0%)
    Dermatitis acneiform 1/12 (8.3%) 0/10 (0%)
    Night sweats 3/12 (25%) 0/10 (0%)
    Onychoclasis 1/12 (8.3%) 0/10 (0%)
    Pruritus 1/12 (8.3%) 4/10 (40%)
    Rash 2/12 (16.7%) 3/10 (30%)
    Rash erythematous 1/12 (8.3%) 0/10 (0%)
    Rash maculo-papular 2/12 (16.7%) 1/10 (10%)
    Skin exfoliation 1/12 (8.3%) 0/10 (0%)
    Vascular disorders
    Hypotension 2/12 (16.7%) 0/10 (0%)

    Limitations/Caveats

    Due to a treatment paradigm shift and subsequent low enrollment, the Sponsor chose to terminate the study and consequently there is limited data. These reasons were unrelated to any adverse events (AEs) or safety concerns. The sample size was smaller than expected, therefore, results should be interpreted with caution. PFS, CRR, and ORR outcomes should be interpreted with caution given large confidence intervals around medians and early study closure.

    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.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please email
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT03138499
    Other Study ID Numbers:
    • CA209-812
    • 2017-000847-41
    First Posted:
    May 3, 2017
    Last Update Posted:
    Apr 12, 2022
    Last Verified:
    Mar 1, 2022