CheckMate 647: A Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02857426
Collaborator
Ono Pharmaceutical Co. Ltd (Industry)
66
Enrollment
50
Locations
2
Arms
49.1
Actual Duration (Months)
1.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Nivolumab is effective in the treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
66 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open-label, Single-arm, Two-cohort Study of Nivolumab in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Relapsed/Refractory Primary Testicular Lymphoma (PTL)
Actual Study Start Date :
Oct 21, 2016
Actual Primary Completion Date :
Jun 11, 2019
Actual Study Completion Date :
Nov 24, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nivolumab for population with PCNSL

Specified dose on specified days

Drug: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
  • Experimental: Nivolumab for population with PTL

    Specified dose on specified days

    Drug: Nivolumab
    Other Names:
  • BMS-936558
  • Opdivo
  • Outcome Measures

    Primary Outcome Measures

    1. BICR-Assessed Objective Response Rate (ORR) [Up to approximately 51 months]

      Percentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.

    Secondary Outcome Measures

    1. BICR-Assessed Progression Free Survival (PFS) [Up to approximately 51 months]

      Progression-free survival (PFS) is defined as the time from first dosing date to the date of the first documented progression using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.

    2. Investigator-Assessed Objective Response Rate (ORR) [Up to approximately 51 months]

      Percentage of participants with a confirmed objective response rate (ORR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.

    3. Investigator-Assessed Duration of Response (DOR) [Up to approximately 51 months]

      Duration of response (DOR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the time from first response (CR or PR) to the date of initial objectively documented progression as determined using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.

    4. Overall Survival (OS) [Up to approximately 51 months]

      Overall survival (OS) was analyzed and reported for both PCNSL and PTL patient populations. OS is defined as the time from first dosing date to the date of death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive.

    Eligibility Criteria

    Criteria

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

    For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

    Inclusion Criteria:
    • Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy

    • Measurable disease requirements on scans:

    PCNSL subjects should have at least one measurable extranodal brain lesion; PTL subjects should have at least 1 measurable extranodal lesion or nodal lesion

    • Have tumor tissue for PD-L1 expression testing

    • Must have a Karnofsky performance status of 70-100

    Exclusion Criteria:
      1. Intraocular PCNSL without evidence of brain disease b) PCNSL patients who cannot undergo MRI assessments c) PCNSL patients with systemic disease
    • Patients with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder

    • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast

    • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

    PCNSL, and PTL subjects with brain or spinal cord lesion who have received doses of more than 2 mg/day of dexamethasone or equivalent within the 14 days period prior to the first dose of nivolumab are excluded

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294-3410
    2City Of Hope Medical CenterDuarteCaliforniaUnited States91010
    3Mayo Clinic JacksonvilleJacksonvilleFloridaUnited States32224
    4H. Lee Moffitt Cancer Center & Research Inst, IncTampaFloridaUnited States33612
    5Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
    6Massachusetts General HospitalBostonMassachusettsUnited States02215
    7Karmanos Cancer InstituteDetroitMichiganUnited States48201
    8Mayo Clinic RochesterRochesterMinnesotaUnited States55905
    9Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    10Columbia UniversityNew YorkNew YorkUnited States10032
    11Fox Chase Cancer CenterPhiladelphiaPennsylvaniaUnited States19111
    12Baylor Research InstituteDallasTexasUnited States75246
    13Swedish Medical CenterSeattleWashingtonUnited States98122
    14Instituto Do Cancer Mae De Deus / Cor Hospital Mae De DeusPorto AlegreRio Grande Do SulBrazil90470-340
    15Fundacao Pio Xii Hosp Cancer De BarretosBarretosSao PauloBrazil14784-400
    16Hospital Das Clinicas - FmuspSao PauloBrazil05403-000
    17BC Cancer Agency - Vancouver CentreVancouverBritish ColumbiaCanadaV5Z 4E6
    18Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9
    19CHU de QuebecQuebecCanadaG1J 1Z4
    20I. interni klinika - klinika hematologie 1. LF UK a VFN v PrazePraha 2Czechia128 08
    21Local InstitutionBordeauxFrance33076
    22Local InstitutionCaenFrance14000
    23Local InstitutionLa TroncheFrance3870
    24Local InstitutionLille CedexFrance59037
    25Local InstitutionParis cedex 13France75651
    26Centre Hospitalier Lyon Sud - UPCOPierre BeniteFrance69495
    27Local InstitutionRennes Cedex 9France35033
    28Local InstitutionSt. CloudFrance92210
    29Local InstitutionTours Cedex 9France37044
    30Klinikum StuttgartStuttgartGermany70174
    31Local InstitutionHong KongHong Kong
    32Local InstitutionBudapestHungary1083
    33Belgyogyaszati Onkologia OOIBudapestHungary1122
    34Local InstitutionDebrecenHungary4032
    35Local InstitutionHaifaIsrael3109601
    36Local InstitutionJerusalemIsrael91120
    37Local InstitutionPetah TikvaIsrael4941492
    38Local InstitutionTel AvivIsrael64239
    39Irccs Ospedale S. RaffaeleMilanoItaly20132
    40Fondazione Policlinico Universitario A. GemelliRomaItaly00168
    41Istituto Clinico HumanitasRozzano (milano)Italy20089
    42Local InstitutionNagoyaAichiJapan4648681
    43Local InstitutionFukuoka-shiFukuokaJapan811-1395
    44Local InstitutionHidaka-shiSaitamaJapan3501298
    45Local InstitutionChuo-kuTokyoJapan1040045
    46Local InstitutionKotokuTokyoJapan1358550
    47Local InstitutionMitaka-shiTokyoJapan181-8611
    48Local InstitutionYamagataJapan9909585
    49Local InstitutionMoscowRussian Federation121309
    50Local InstitutionSingaporeSingapore169610

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • 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:
    NCT02857426
    Other Study ID Numbers:
    • CA209-647
    • 2016-000894-19
    First Posted:
    Aug 5, 2016
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail47 PCNSL participants treated. 19 PTL participants treated.
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Period Title: Overall Study
    STARTED4719
    COMPLETED00
    NOT COMPLETED4719

    Baseline Characteristics

    Arm/Group TitlePCNSL CohortPTL CohortTotal
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Total of all reporting groups
    Overall Participants471966
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.9
    (10.1)
    66.7
    (8.6)
    66.1
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    20
    42.6%
    0
    0%
    20
    30.3%
    Male
    27
    57.4%
    19
    100%
    46
    69.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    2.1%
    0
    0%
    1
    1.5%
    Not Hispanic or Latino
    33
    70.2%
    11
    57.9%
    44
    66.7%
    Unknown or Not Reported
    13
    27.7%
    8
    42.1%
    21
    31.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    10
    21.3%
    5
    26.3%
    15
    22.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    37
    78.7%
    12
    63.2%
    49
    74.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    2
    10.5%
    2
    3%

    Outcome Measures

    1. Primary Outcome
    TitleBICR-Assessed Objective Response Rate (ORR)
    DescriptionPercentage of participants with a confirmed objective response rate (ORR) by blinded independent central review (BICR) assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.
    Time FrameUp to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants4719
    Number (95% Confidence Interval) [Percentage of participants]
    6.4
    13.6%
    26.3
    138.4%
    2. Secondary Outcome
    TitleBICR-Assessed Progression Free Survival (PFS)
    DescriptionProgression-free survival (PFS) is defined as the time from first dosing date to the date of the first documented progression using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
    Time FrameUp to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants4719
    Median (95% Confidence Interval) [Months]
    1.41
    1.72
    3. Secondary Outcome
    TitleInvestigator-Assessed Objective Response Rate (ORR)
    DescriptionPercentage of participants with a confirmed objective response rate (ORR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, divided by the number of treated participants within each cohort.
    Time FrameUp to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants4719
    Number (95% Confidence Interval) [Percentage of participants]
    10.6
    22.6%
    26.3
    138.4%
    4. Secondary Outcome
    TitleInvestigator-Assessed Duration of Response (DOR)
    DescriptionDuration of response (DOR) by investigator assessment was analyzed and reported for both PCNSL and PTL patient populations. This endpoint is further defined as the time from first response (CR or PR) to the date of initial objectively documented progression as determined using the IPCG Criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first.
    Time FrameUp to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All responders PCNSL and PTL participants
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants55
    Median (95% Confidence Interval) [Months]
    1.71
    20.63
    5. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOverall survival (OS) was analyzed and reported for both PCNSL and PTL patient populations. OS is defined as the time from first dosing date to the date of death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive.
    Time FrameUp to approximately 51 months

    Outcome Measure Data

    Analysis Population Description
    All treated PCNSL and PTL participants
    Arm/Group TitlePCNSL CohortPTL Cohort
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    Measure Participants4719
    Median (95% Confidence Interval) [Months]
    6.77
    11.17

    Adverse Events

    Time FrameFrom first dose to 100 days post last dose (up to approximately 48 months)
    Adverse Event Reporting Description
    Arm/Group TitlePCNSL Cohort Nivolumab 240 mg (Q2W)PTL Cohort Nivolumab 240 mg (Q2W)
    Arm/Group DescriptionNivolumab dosed to participants with relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.Nivolumab dosed to participants with relapsed/refractory Primary Testicular Lymphoma (PTL). Nivolumab 240 mg was given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg was given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab was administered as a 30-minute infusion.
    All Cause Mortality
    PCNSL Cohort Nivolumab 240 mg (Q2W)PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total32/47 (68.1%) 13/19 (68.4%)
    Serious Adverse Events
    PCNSL Cohort Nivolumab 240 mg (Q2W)PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total33/47 (70.2%) 15/19 (78.9%)
    Blood and lymphatic system disorders
    Anaemia0/47 (0%) 1/19 (5.3%)
    Febrile neutropenia1/47 (2.1%) 1/19 (5.3%)
    Leukopenia1/47 (2.1%) 0/19 (0%)
    Pancytopenia1/47 (2.1%) 0/19 (0%)
    Gastrointestinal disorders
    Dysphagia1/47 (2.1%) 0/19 (0%)
    General disorders
    Asthenia1/47 (2.1%) 0/19 (0%)
    Fatigue1/47 (2.1%) 0/19 (0%)
    Gait disturbance1/47 (2.1%) 0/19 (0%)
    General physical health deterioration2/47 (4.3%) 1/19 (5.3%)
    Mucosal inflammation1/47 (2.1%) 0/19 (0%)
    Pyrexia1/47 (2.1%) 1/19 (5.3%)
    Sudden death1/47 (2.1%) 0/19 (0%)
    Hepatobiliary disorders
    Hepatitis0/47 (0%) 1/19 (5.3%)
    Hepatitis acute1/47 (2.1%) 0/19 (0%)
    Infections and infestations
    Cystitis0/47 (0%) 1/19 (5.3%)
    Influenza1/47 (2.1%) 0/19 (0%)
    Meningitis viral1/47 (2.1%) 0/19 (0%)
    Pneumonia0/47 (0%) 1/19 (5.3%)
    Pulmonary sepsis1/47 (2.1%) 0/19 (0%)
    Sepsis3/47 (6.4%) 0/19 (0%)
    Septic shock1/47 (2.1%) 0/19 (0%)
    Urinary tract infection1/47 (2.1%) 0/19 (0%)
    Vascular device infection0/47 (0%) 1/19 (5.3%)
    Injury, poisoning and procedural complications
    Cervical vertebral fracture1/47 (2.1%) 0/19 (0%)
    Fall2/47 (4.3%) 1/19 (5.3%)
    Hip fracture1/47 (2.1%) 0/19 (0%)
    Infusion related reaction1/47 (2.1%) 0/19 (0%)
    Investigations
    Lymphocyte count decreased1/47 (2.1%) 0/19 (0%)
    Neutrophil count decreased1/47 (2.1%) 0/19 (0%)
    Platelet count decreased1/47 (2.1%) 0/19 (0%)
    Metabolism and nutrition disorders
    Dehydration2/47 (4.3%) 0/19 (0%)
    Failure to thrive1/47 (2.1%) 0/19 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/47 (0%) 1/19 (5.3%)
    Muscular weakness1/47 (2.1%) 0/19 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon0/47 (0%) 1/19 (5.3%)
    Lung adenocarcinoma0/47 (0%) 1/19 (5.3%)
    Malignant neoplasm progression13/47 (27.7%) 8/19 (42.1%)
    Tumour flare2/47 (4.3%) 0/19 (0%)
    Tumour pseudoprogression1/47 (2.1%) 0/19 (0%)
    Nervous system disorders
    Brain oedema1/47 (2.1%) 0/19 (0%)
    Cognitive disorder1/47 (2.1%) 0/19 (0%)
    Depressed level of consciousness2/47 (4.3%) 0/19 (0%)
    Encephalopathy2/47 (4.3%) 0/19 (0%)
    Epilepsy1/47 (2.1%) 0/19 (0%)
    Haemorrhage intracranial3/47 (6.4%) 0/19 (0%)
    Headache2/47 (4.3%) 0/19 (0%)
    Hemianopia homonymous1/47 (2.1%) 0/19 (0%)
    Hemiparesis1/47 (2.1%) 0/19 (0%)
    Hemiplegia1/47 (2.1%) 0/19 (0%)
    Mental impairment1/47 (2.1%) 0/19 (0%)
    Nervous system disorder1/47 (2.1%) 0/19 (0%)
    Neurological decompensation2/47 (4.3%) 0/19 (0%)
    Optic neuritis0/47 (0%) 1/19 (5.3%)
    Seizure4/47 (8.5%) 1/19 (5.3%)
    Syncope1/47 (2.1%) 0/19 (0%)
    Psychiatric disorders
    Confusional state2/47 (4.3%) 0/19 (0%)
    Mental status changes1/47 (2.1%) 0/19 (0%)
    Renal and urinary disorders
    Acute kidney injury0/47 (0%) 1/19 (5.3%)
    Renal failure1/47 (2.1%) 2/19 (10.5%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism1/47 (2.1%) 0/19 (0%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme1/47 (2.1%) 0/19 (0%)
    Other (Not Including Serious) Adverse Events
    PCNSL Cohort Nivolumab 240 mg (Q2W)PTL Cohort Nivolumab 240 mg (Q2W)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total40/47 (85.1%) 16/19 (84.2%)
    Blood and lymphatic system disorders
    Anaemia13/47 (27.7%) 1/19 (5.3%)
    Thrombocytopenia4/47 (8.5%) 1/19 (5.3%)
    Cardiac disorders
    Bradycardia2/47 (4.3%) 1/19 (5.3%)
    Tachycardia0/47 (0%) 1/19 (5.3%)
    Ear and labyrinth disorders
    Tinnitus1/47 (2.1%) 1/19 (5.3%)
    Vertigo3/47 (6.4%) 0/19 (0%)
    Eye disorders
    Conjunctival hyperaemia0/47 (0%) 1/19 (5.3%)
    Dry eye0/47 (0%) 1/19 (5.3%)
    Eye irritation1/47 (2.1%) 1/19 (5.3%)
    Glaucoma0/47 (0%) 2/19 (10.5%)
    Pupils unequal0/47 (0%) 1/19 (5.3%)
    Vision blurred1/47 (2.1%) 1/19 (5.3%)
    Gastrointestinal disorders
    Constipation8/47 (17%) 4/19 (21.1%)
    Diarrhoea5/47 (10.6%) 2/19 (10.5%)
    Dry mouth0/47 (0%) 2/19 (10.5%)
    Dysphagia3/47 (6.4%) 0/19 (0%)
    Haematochezia0/47 (0%) 1/19 (5.3%)
    Nausea6/47 (12.8%) 2/19 (10.5%)
    Stomatitis3/47 (6.4%) 0/19 (0%)
    Vomiting7/47 (14.9%) 0/19 (0%)
    General disorders
    Asthenia2/47 (4.3%) 2/19 (10.5%)
    Fatigue12/47 (25.5%) 2/19 (10.5%)
    Gait disturbance6/47 (12.8%) 1/19 (5.3%)
    Mucosal inflammation2/47 (4.3%) 1/19 (5.3%)
    Non-cardiac chest pain3/47 (6.4%) 1/19 (5.3%)
    Oedema peripheral3/47 (6.4%) 2/19 (10.5%)
    Pyrexia9/47 (19.1%) 5/19 (26.3%)
    Hepatobiliary disorders
    Hepatic steatosis0/47 (0%) 1/19 (5.3%)
    Hepatitis0/47 (0%) 1/19 (5.3%)
    Hepatotoxicity0/47 (0%) 1/19 (5.3%)
    Infections and infestations
    Bronchitis0/47 (0%) 1/19 (5.3%)
    Cellulitis1/47 (2.1%) 1/19 (5.3%)
    Clostridium difficile infection1/47 (2.1%) 1/19 (5.3%)
    Gastroenteritis1/47 (2.1%) 1/19 (5.3%)
    Herpes simplex0/47 (0%) 1/19 (5.3%)
    Influenza0/47 (0%) 1/19 (5.3%)
    Oral candidiasis1/47 (2.1%) 1/19 (5.3%)
    Pneumonia2/47 (4.3%) 1/19 (5.3%)
    Upper respiratory tract infection1/47 (2.1%) 1/19 (5.3%)
    Urinary tract infection5/47 (10.6%) 0/19 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture0/47 (0%) 1/19 (5.3%)
    Clavicle fracture0/47 (0%) 1/19 (5.3%)
    Fall9/47 (19.1%) 3/19 (15.8%)
    Infusion related reaction2/47 (4.3%) 1/19 (5.3%)
    Procedural pain0/47 (0%) 1/19 (5.3%)
    Recall phenomenon0/47 (0%) 1/19 (5.3%)
    Upper limb fracture0/47 (0%) 1/19 (5.3%)
    Investigations
    Alanine aminotransferase increased10/47 (21.3%) 1/19 (5.3%)
    Aspartate aminotransferase increased7/47 (14.9%) 1/19 (5.3%)
    Blood creatinine increased3/47 (6.4%) 1/19 (5.3%)
    Human rhinovirus test positive0/47 (0%) 1/19 (5.3%)
    Lipase increased3/47 (6.4%) 1/19 (5.3%)
    Lymphocyte count decreased6/47 (12.8%) 0/19 (0%)
    Neutrophil count decreased5/47 (10.6%) 1/19 (5.3%)
    Platelet count decreased5/47 (10.6%) 1/19 (5.3%)
    Weight decreased4/47 (8.5%) 0/19 (0%)
    White blood cell count decreased3/47 (6.4%) 1/19 (5.3%)
    Metabolism and nutrition disorders
    Decreased appetite5/47 (10.6%) 0/19 (0%)
    Dehydration3/47 (6.4%) 0/19 (0%)
    Hyperglycaemia6/47 (12.8%) 1/19 (5.3%)
    Hypernatraemia3/47 (6.4%) 1/19 (5.3%)
    Hypoalbuminaemia5/47 (10.6%) 0/19 (0%)
    Hypocalcaemia5/47 (10.6%) 0/19 (0%)
    Hypokalaemia5/47 (10.6%) 1/19 (5.3%)
    Hyponatraemia7/47 (14.9%) 0/19 (0%)
    Hypophosphataemia4/47 (8.5%) 0/19 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia2/47 (4.3%) 4/19 (21.1%)
    Arthritis1/47 (2.1%) 1/19 (5.3%)
    Back pain4/47 (8.5%) 0/19 (0%)
    Bursitis0/47 (0%) 1/19 (5.3%)
    Muscular weakness4/47 (8.5%) 2/19 (10.5%)
    Musculoskeletal chest pain1/47 (2.1%) 1/19 (5.3%)
    Myalgia1/47 (2.1%) 1/19 (5.3%)
    Pain in extremity3/47 (6.4%) 1/19 (5.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression1/47 (2.1%) 1/19 (5.3%)
    Nervous system disorders
    Aphasia5/47 (10.6%) 0/19 (0%)
    Ataxia4/47 (8.5%) 0/19 (0%)
    Dizziness4/47 (8.5%) 0/19 (0%)
    Dysaesthesia0/47 (0%) 1/19 (5.3%)
    Facial paresis3/47 (6.4%) 0/19 (0%)
    Headache12/47 (25.5%) 1/19 (5.3%)
    Hemiparesis5/47 (10.6%) 0/19 (0%)
    Paraesthesia3/47 (6.4%) 0/19 (0%)
    Seizure6/47 (12.8%) 0/19 (0%)
    Somnolence3/47 (6.4%) 0/19 (0%)
    Psychiatric disorders
    Agitation3/47 (6.4%) 0/19 (0%)
    Anxiety4/47 (8.5%) 0/19 (0%)
    Confusional state4/47 (8.5%) 1/19 (5.3%)
    Depression3/47 (6.4%) 0/19 (0%)
    Insomnia5/47 (10.6%) 1/19 (5.3%)
    Renal and urinary disorders
    Acute kidney injury0/47 (0%) 1/19 (5.3%)
    Chronic kidney disease1/47 (2.1%) 1/19 (5.3%)
    Urinary incontinence5/47 (10.6%) 0/19 (0%)
    Reproductive system and breast disorders
    Testicular pain0/47 (0%) 1/19 (5.3%)
    Testicular swelling0/47 (0%) 1/19 (5.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough3/47 (6.4%) 2/19 (10.5%)
    Dyspnoea3/47 (6.4%) 1/19 (5.3%)
    Pleural effusion1/47 (2.1%) 1/19 (5.3%)
    Pneumonitis1/47 (2.1%) 1/19 (5.3%)
    Skin and subcutaneous tissue disorders
    Dermal cyst0/47 (0%) 1/19 (5.3%)
    Eczema asteatotic0/47 (0%) 1/19 (5.3%)
    Hyperhidrosis0/47 (0%) 1/19 (5.3%)
    Pruritus7/47 (14.9%) 1/19 (5.3%)
    Rash4/47 (8.5%) 2/19 (10.5%)
    Rash maculo-papular1/47 (2.1%) 3/19 (15.8%)
    Skin ulcer0/47 (0%) 1/19 (5.3%)
    Vascular disorders
    Hypotension0/47 (0%) 1/19 (5.3%)

    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.

    Results Point of Contact

    Name/TitleBristol-Myers Squibb Study Director
    OrganizationBristol-Myers Squibb
    PhonePlease Email:
    EmailClinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02857426
    Other Study ID Numbers:
    • CA209-647
    • 2016-000894-19
    First Posted:
    Aug 5, 2016
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Nov 1, 2021