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    Clinical Trial Results:
    Randomized, Non-comparative Neoadjuvant Phase II Study in Patients with ER+/HER2- Breast Cancer ≥ 2 cm with Safety Run-in, Assessing Nivolumab + Palbociclib + Anastrozole (CheckMate 7A8: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 7A8)

    Summary
    EudraCT number
    		 2019-001334-34
    Trial protocol
    		 FR   DE   BE   ES  
    Global end of trial date
    27 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2022
    First version publication date
    30 Jul 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CA209-7A8
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04075604
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective is to determine the number of participants with occurrence of DLTs in the Safety Run-in Phase and to estimate the RCB (0-I) rate per central assessment in participants in each randomized arm during the Randomized phase.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Oct 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 14
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Spain: 5
    Worldwide total number of subjects
    23
    EEA total number of subjects
    9
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    13
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 23 participants were randomized and treated during the study

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Dose level 1
    Arm description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Abemaciclib: 150 mg twice daily (BID) per os (by mouth) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg every 4 weeks

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg once daily

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg twice daily

    Arm title
    		 Cohort 2: Dose level 1
    Arm description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 125 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    125 mg once daily

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg once daily

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg every 4 weeks

    Arm title
    		 Cohort 2: Dose level 2
    Arm description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 100 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg every 4 weeks

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg once daily

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg once daily

    Number of subjects in period 1
    		Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Started
    2
    9
    12
    Completed
    1
    3
    6
    Not completed
    1
    6
    6
         Disease progression
    -
    1
    -
         Participant withdrew consent
    -
    -
    1
         Study drug toxicity
    -
    5
    1
         Adverse event, non-fatal
    -
    -
    3
         Other reasons
    1
    -
    -
         Participant request to discontinue study treatment
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Abemaciclib: 150 mg twice daily (BID) per os (by mouth) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 125 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 2
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 100 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2 Total
    Number of subjects
    		 2 9 12 23
    Age Categorical
    Units: Participants
        < 65
    		 1 7 5 13
        >= 65 AND < 75
    		 1 1 3 5
        >= 75 AND < 85
    		 0 1 4 5
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 63 ± 2.8 60.3 ± 9.3 67.4 ± 10.2 -
    Sex: Female, Male
    Units: Participants
        Female
    		 2 9 12 23
        Male
    		 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 0 0 1 1
        White
    		 1 9 11 21
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 1 0 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 2 2 4
        Not Hispanic or Latino
    		 2 5 7 14
        Unknown or Not Reported
    		 0 2 3 5

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Abemaciclib: 150 mg twice daily (BID) per os (by mouth) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 125 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 2
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 100 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Primary: The Number of Participants with Dose Limiting Toxicities (DLT) in the Safety Run-in Phase

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    End point title
    		 The Number of Participants with Dose Limiting Toxicities (DLT) in the Safety Run-in Phase [1]
    End point description
    The number of participants with dose limiting toxicities (DLTs) during the safety run-in phase. DLTS are defined as treatment emergent adverse events (TEAE) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 that occurs during the first 4 weeks (1 cycle) after treatment. Participants who withdraw from the study during the DLT evaluation period or have received less than 1 dose of nivolumab and 75% of accumulative doses of palbociclib of the cycle for reasons other than a DLT will not be considered as DLT-evaluable participants.
    End point type
    Primary
    End point timeframe
    From first dose to 4 weeks after first dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics planned for this endpoint
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    1
    9
    12
    Units: Participants
    0
    2
    0
    No statistical analyses for this end point

    Primary: Residual Cancer Burden (RCB) 0-1 Rate in the Randomized Phase

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    End point title
    		 Residual Cancer Burden (RCB) 0-1 Rate in the Randomized Phase [2]
    End point description
    RCB 0-I rate is defined as the percentage of randomized participants who achieve RCB 0: no residual disease or RCB-I: minimal residual disease. RCB is a continuous index combining pathological measurements of primary tumor (size and cellularity) and nodal metastases (number and size) defined by a point system at surgery.
    End point type
    Primary
    End point timeframe
    From randomization phase up to 5 treatment cycles (up to approximately 20 weeks)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics planned for this endpoint
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    Units: Percent of Participant
    Notes
    [3] - Trial closed after completion of the Safety Run-in.
    [4] - Trial closed after completion of the Safety Run-in.
    [5] - Trial closed after completion of the Safety Run-in.
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR)
    End point description
    ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per investigator radiographic assessment. Complete response 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. Partial response (PR) is defines as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From first dose up to approximately 6 months after first dose
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Percentage of Participants
        number (confidence interval 95%)
    0.0 (0.0 to 84.2)
    66.7 (29.9 to 92.5)
    75.0 (42.8 to 94.5)
    No statistical analyses for this end point

    Secondary: Breast Conserving Surgery (BCS) Rate

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    End point title
    		 Breast Conserving Surgery (BCS) Rate
    End point description
    The percentage of participants who undergo breast conserving surgery (BCS) after completing the study treatments. Confidence interval based on the Clopper and Pearson method.
    End point type
    Secondary
    End point timeframe
    From first dose up to approximately 6 months after first dose
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Percentage of Participants
        number (confidence interval 95%)
    50.0 (1.3 to 98.7)
    55.6 (21.2 to 86.3)
    50.0 (21.1 to 78.9)
    No statistical analyses for this end point

    Secondary: Pathological Complete Response (pCR) Rate

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    End point title
    		 Pathological Complete Response (pCR) Rate
    End point description
    The percentage of participants with an absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Confidence interval based on the Clopper and Pearson method.
    End point type
    Secondary
    End point timeframe
    From first dose up to approximately 6 months after first dose
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Percentage of Participants
        number (confidence interval 95%)
    0.0 (0.0 to 84.2)
    0.0 (0.0 to 33.6)
    8.3 (0.2 to 38.5)
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Adverse Events (AEs)

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    End point title
    		 The Number of Participants Experiencing Adverse Events (AEs)
    End point description
    The number of participants experiencing adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
    2
    9
    12
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Serious Adverse Events (SAEs)

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    End point title
    		 The Number of Participants Experiencing Serious Adverse Events (SAEs)
    End point description
    The number of participants experiencing serious adverse events (SAEs). A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
    0
    5
    2
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

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    End point title
    		 The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
    End point description
    The number of participants experiencing adverse events (AEs) that lead to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
    0
    5
    4
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Immune-Related Adverse Events (AEs)

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    End point title
    		 The Number of Participants Experiencing Immune-Related Adverse Events (AEs)
    End point description
    The number of participants experiencing adverse events that are immune-related. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    From first dose to 100 days after last dose of study therapy (up to approximately 8 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    1
    9
    12
    Units: Participants
        Hypothyroidism
    1
    0
    0
        Hyperthyroidism
    0
    0
    1
        Immune-mediated lung disease
    0
    1
    0
        Pneumonitis
    0
    0
    1
        Hepatitis
    0
    3
    2
        Rash
    0
    2
    0
    No statistical analyses for this end point

    Secondary: The Number of Participants Deaths

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    End point title
    		 The Number of Participants Deaths
    End point description
    The number of participants that have died during the study.
    End point type
    Secondary
    End point timeframe
    From first dose up to approximately 8 months
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
    0
    0
    0
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests - SI Units

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    End point title
    		 The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests - SI Units
    End point description
    The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
        TSH > ULN
    1
    3
    2
        TSH > ULN WITH TSH <= ULN AT BASELINE
    1
    2
    1
        TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
    0
    1
    2
        TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN
    0
    2
    2
        TSH > ULN WITH FT3/FT4 TEST MISSING
    1
    0
    0
        TSH < LLN
    0
    3
    4
        TSH <LLN WITH TSH >= LLN AT BASELINE
    0
    2
    4
        TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
    0
    1
    1
        TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN
    0
    1
    3
        TSH < LLN WITH FT3/FT4 TEST MISSING
    0
    1
    0
    No statistical analyses for this end point

    Secondary: The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests

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    End point title
    		 The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
    End point description
    The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
    End point values
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 1 Cohort 2: Dose level 2
    Number of subjects analysed
    2
    9
    12
    Units: Participants
        ALT OR AST > 3XULN
    0
    4
    3
        ALT OR AST > 5XULN
    0
    3
    3
        ALT OR AST > 10XULN
    0
    2
    2
        ALT OR AST > 20XULN
    0
    1
    2
        TOTAL BILIRUBIN > 2XULN
    0
    0
    0
        ALP > 1.5XULN
    0
    3
    1
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN-1 DAY
    0
    1
    1
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN-30 DAYS
    0
    1
    1
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN-1 DAY
    0
    0
    0
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN-30 DAYS
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs assessed from first dose to 100 days after last dose (up to 8 months). SAEs assessed from first dose to 30 days after last dose (Up to 6 months). All-Cause Mortality assessed from first dose to study completion (up to 21 months).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Cohort 1: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Abemaciclib: 150 mg twice daily (BID) per os (by mouth) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 2
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 100 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Reporting group title
    Cohort 2: Dose level 1
    Reporting group description
    		 Nivolumab: 480 mg every 4 weeks (Q4W) intravenously (IV) Palbociclib: 125 mg once daily (QD) per os (by mouth) for 3 weeks of each cycle (1 week off) Anastrozole: 1 mg once daily (QD) per os (by mouth) Participants will be treated for a maximum of 5 cycles (1 cycle = 4 weeks)

    Serious adverse events
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 2 Cohort 2: Dose level 1
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 12 (25.00%)
    5 / 9 (55.56%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Second primary malignancy
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Dose level 1 Cohort 2: Dose level 2 Cohort 2: Dose level 1
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    12 / 12 (100.00%)
    8 / 9 (88.89%)
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 2 (0.00%)
    4 / 12 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    4
    0
    Axillary pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Fatigue
         subjects affected / exposed
    1 / 2 (50.00%)
    5 / 12 (41.67%)
    2 / 9 (22.22%)
         occurrences all number
    1
    8
    2
    Mucosal inflammation
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    1
    Pyrexia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Xerosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    1
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    1
    Pneumonitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    4 / 9 (44.44%)
         occurrences all number
    0
    2
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    4 / 9 (44.44%)
         occurrences all number
    0
    2
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    3
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    3
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    5 / 12 (41.67%)
    1 / 9 (11.11%)
         occurrences all number
    0
    8
    2
    Platelet count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    3
    1
    Transaminases increased
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 12 (25.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    3
    4
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Radiation skin injury
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Vascular access site pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    2
    Dysgeusia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Sinus headache
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    1
    3
    Leukopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Macrocytosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    1
    Neutropenia
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 12 (25.00%)
    3 / 9 (33.33%)
         occurrences all number
    0
    3
    4
    Thrombocytopenia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    1
    Thrombocytosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Eye disorders
    Ocular discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Vision blurred
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    2 / 9 (22.22%)
         occurrences all number
    1
    1
    2
    Dyspepsia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    3
    0
    Nausea
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    1
    Odynophagia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Oral pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Eczema
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    2 / 2 (100.00%)
    3 / 12 (25.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    3
    1
    Rash
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    3 / 9 (33.33%)
         occurrences all number
    1
    1
    4
    Skin toxicity
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Rash pruritic
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 2 (50.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    1
    2
    0
    Back pain
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Bone pain
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    1
    0
    2
    Muscle spasms
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    2
    Musculoskeletal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Diverticulitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Viral infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    2
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    1
    2
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
         occurrences all number
    0
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Jun 2019
    Decreased and clarified the frequency of assessments and sample collections, clarified participant eligibility and stratification, and reduced the dose-limiting toxicity period.
    24 Jul 2019
    Added men, additional dose-limiting toxicity (DLT) criteria, and early study termination criteria. Updated definition of DLT, inclusion/exclusion criteria, and dose modifications.
    13 May 2020
    Closed the abemaciclib safety run-in Cohort 1 and removed the abemaciclib-containing combinations from the randomization phase.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Enrollment/dosing in Cohort 1 was discontinued due to risk of serious interstitial lung disease/pneumonitis in patients receiving abemaciclib with pembrolizumab. The trial closed after completion of the Safety Run-in.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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