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    Clinical Trial Results:
    A Randomized, Double-blind, Adaptive, Phase II/III Study of GSK3359609 or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1 Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

    Summary
    EudraCT number
    		 2019-002263-99
    Trial protocol
    		 NL   GB   IE   SE   DE   PL   DK   AT   NO   HU   GR   PT   ES   IT   RO  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 May 2022
    First version publication date
    12 May 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    209229
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04128696
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.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
    Interim
    Date of interim/final analysis
    27 Apr 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Apr 2021
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To evaluate if the addition of feladilimab to pembrolizumab as first-line treatment improves the efficacy of pembrolizumab in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma/cancer (HNSCC).
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Nov 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 1
    Country: Number of subjects enrolled
    Australia: 20
    Country: Number of subjects enrolled
    Brazil: 10
    Country: Number of subjects enrolled
    Canada: 31
    Country: Number of subjects enrolled
    China: 16
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    France: 21
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Japan: 20
    Country: Number of subjects enrolled
    Korea, Republic of: 18
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    Netherlands: 7
    Country: Number of subjects enrolled
    Norway: 6
    Country: Number of subjects enrolled
    Poland: 26
    Country: Number of subjects enrolled
    Portugal: 5
    Country: Number of subjects enrolled
    Romania: 29
    Country: Number of subjects enrolled
    Russian Federation: 18
    Country: Number of subjects enrolled
    Spain: 13
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    United States: 25
    Worldwide total number of subjects
    315
    EEA total number of subjects
    129
    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)
    174
    From 65 to 84 years
    138
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 As of cut off date a total of 315 participants with HNSCC were enrolled in this study. Of which, 2 were dosed only with pembrolizumab after the date of Dear Investigator Letter (DIL). Hence, 313 participants were included in the modified Intent to Treat (mITT) population and 315 participants were included in the safety and enrolled populations.

    Pre-assignment
    Screening details
    		 Recruitment in the study was stopped following review by of interim safety and efficacy data after a pre-specified futility analysis. Participants discontinued feladilimab/placebo, but treatment with pembrolizumab will continue until disease progression, death or unacceptable toxicity and safety data will be updated following study end.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Participants receiving feladilimab and pembrolizumab
    Arm description
    		 Participants were administered feladilimab (GSK3359609-humanized anti-ICOS immunoglobulin G4 [IgG4] monoclonal antibody [mAb]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks(Q3W).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Feladilimab+ Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants were administered feladilimab in combination with pembrolizumab as an intravenous infusion over approximately 30 minutes every Q3W.

    Arm title
    		 Participants receiving placebo and pembrolizumab
    Arm description
    		 Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo+ Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants were administered placebo in combination with pembrolizumabas an intravenous infusion over approximately 30 minutes every Q3W.

    Number of subjects in period 1
    		Participants receiving feladilimab and pembrolizumab Participants receiving placebo and pembrolizumab
    Started
    158
    157
    mITT population
    157
    156
    Completed
    51
    38
    Not completed
    107
    119
         On Study Treatment (Pembrolizumab)
    52
    62
         Consent withdrawn by subject
    8
    5
         Lost to follow-up
    -
    1
         In Follow-up
    47
    51

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Participants receiving feladilimab and pembrolizumab
    Reporting group description
    		 Participants were administered feladilimab (GSK3359609-humanized anti-ICOS immunoglobulin G4 [IgG4] monoclonal antibody [mAb]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks(Q3W).

    Reporting group title
    Participants receiving placebo and pembrolizumab
    Reporting group description
    		 Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W.

    Reporting group values
    		 Participants receiving feladilimab and pembrolizumab Participants receiving placebo and pembrolizumab Total
    Number of subjects
    		 158 157 315
    Age Categorical
    Units:
        18-64 years
    		 95 79 174
        >=65-84 years
    		 62 76 138
        >=85 years
    		 1 2 3
    Sex: Female, Male
    Units: Participants
        Female
    		 29 31 60
        Male
    		 129 126 255
    Race/Ethnicity, Customized
    Units: Subjects
        Asian - Central/South Asian Heritage
    		 2 0 2
        Asian - East Asian Heritage
    		 19 22 41
        Asian - Japanese Heritage
    		 12 7 19
        Black or African American
    		 4 2 6
        Missing
    		 3 6 9
        Mixed White Race
    		 1 1 2
        Multiple
    		 1 0 1
        White - Arabic/North African Heritage
    		 4 1 5
        White - White/Caucasian/European Heritage
    		 111 118 229
        Native Hawaiian or Other Pacific Islander
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Participants receiving feladilimab and pembrolizumab
    Reporting group description
    		 Participants were administered feladilimab (GSK3359609-humanized anti-ICOS immunoglobulin G4 [IgG4] monoclonal antibody [mAb]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks(Q3W).

    Reporting group title
    Participants receiving placebo and pembrolizumab
    Reporting group description
    		 Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W.

    Subject analysis set title
    Feladilimab + pembrolizumab safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized participants who took at least 1 dose of study intervention. Participants were assigned to the actual study intervention group of feladilimab + pembrolizumab if the participant received any dose of feladilimab. Participants were analyzed according to the actual study intervention received.

    Subject analysis set title
    Placebo + pembrolizumab safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized participants who took at least 1 dose of study intervention. Participants were assigned to the actual study intervention group of feladilimab + pembrolizumab if the participant received any dose of feladilimab. Participants were analyzed according to the actual study intervention received.

    Subject analysis set title
    Feladilimab +pembrolizumab mITT analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized participants whether or not randomized intervention was administered, excluding those who were first dosed or randomized after the date of DIL requesting immediate discontinuation of feladilimab /placebo. This analysis set was based on the study intervention to which the participant was randomized.

    Subject analysis set title
    Placebo + pembrolizumab mITT analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized participants whether or not randomized intervention was administered, excluding those who were first dosed or randomized after the date of DIL requesting immediate discontinuation of feladilimab /placebo. This analysis set was based on the study intervention to which the participant was randomized.

    Primary: Overall survival (OS) in the PD-L1 expression positive (Combined positive score [CPS] ≥1) population

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    End point title
    		 Overall survival (OS) in the PD-L1 expression positive (Combined positive score [CPS] ≥1) population
    End point description
    OS was defined as the time from the date of randomization to the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants in the mITT population with CPS ≥1 are presented here. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. 99999 = The median was not reached at the time of primary completion date and the upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Primary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Week
        median (confidence interval 95%)
    44.1 (35.9 to 99999)
    99999 (52.4 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.973 [1]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 2.29
    Notes
    [1] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)

    Primary: OS in the PD-L1 expression high (CPS ≥20) population

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    End point title
    		 OS in the PD-L1 expression high (CPS ≥20) population
    End point description
    OS was defined as the time from the date of randomization to the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants who had a PD-L1 CPS of ≥20 are presented here. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. 99999 = The median was not reached at the time of primary completion date and the upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Primary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Week
        median (confidence interval 95%)
    42.1 (25.4 to 99999)
    99999 (52.4 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 > 0.999 [2]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    4.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.01
         upper limit
    		 9.82
    Notes
    [2] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Primary: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 population

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    End point title
    		 Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 population
    End point description
    PFS per RECIST version (v)1.1 was defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants in the mITT population with CPS ≥1 are presented here. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
    End point type
    Primary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Week
        median (confidence interval 95%)
    10.1 (9.1 to 15.0)
    16.0 (14.3 to 26.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.989 [3]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 1.86
    Notes
    [3] - Nominal P-value was calculated based on the one-sided log-rank test, stratified by stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Secondary: PFS per immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 population

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    End point title
    		 PFS per immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 population
    End point description
    PFS per iRECIST was defined as the interval of time from the date of randomization to the date of the first documented disease progression confirmed consecutively per iRECIST based on investigator assessment, or death due to any cause, whichever occurs first. Data for participants in the mITT population with CPS ≥1 are presented here. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Week
        median (confidence interval 95%)
    13.0 (9.1 to 15.0)
    21.4 (15.6 to 27.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.996 [4]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 1.99
    Notes
    [4] - Nominal P-value was calculated based on the one-sided log-rank test, stratified by stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Secondary: PFS per RECIST in the PD-L1 CPS ≥20 population

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    End point title
    		 PFS per RECIST in the PD-L1 CPS ≥20 population
    End point description
    PFS per RECIST v1.1 was defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants who had a PD-L1 CPS of ≥20 are presented here. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Week
        median (confidence interval 95%)
    13.0 (8.6 to 26.1)
    21.1 (15.6 to 32.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 2.43

    Secondary: PFS per iRECIST (iPFS) in the PD-L1 CPS ≥20 population

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    End point title
    		 PFS per iRECIST (iPFS) in the PD-L1 CPS ≥20 population
    End point description
    PFS per iRECIST was defined as the interval of time from the date of randomization to the date of the first documented disease progression confirmed consecutively per iRECIST based on investigator assessment, or death due to any cause, whichever occurs first. Data for participants who had a PD-L1 CPS of ≥20 are presented here. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Week
        median (confidence interval 95%)
    13.1 (8.6 to 26.7)
    26.7 (20.1 to 32.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 2.53

    Secondary: Milestone OS rate at 12 months in the PD-L1 CPS ≥1 population

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    End point title
    		 Milestone OS rate at 12 months in the PD-L1 CPS ≥1 population
    End point description
    Milestone OS rate at 12 months was estimated using the Kaplan-Meier method. Associated 95% confidence intervals are estimated using the Brookmeyer-Crowley method. Data for participants in the mITT population with CPS ≥1 are presented here. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Percentage of Participants
        number (confidence interval 95%)
    44 (30 to 58)
    68 (57 to 77)
    No statistical analyses for this end point

    Secondary: Milestone OS rate at 24 months in the PD-L1 CPS ≥1 population

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    End point title
    		 Milestone OS rate at 24 months in the PD-L1 CPS ≥1 population
    End point description
    Milestone OS rate at 24 months was not evaluated. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    0 [5]
    0 [6]
    Units: Percentage of participants
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [5] - No participant had follow-up duration exceeding 24 months.
    [6] - No participant had follow-up duration exceeding 24 months.
    No statistical analyses for this end point

    Secondary: Milestone OS rate at 12 months in the PD-L1 CPS ≥20 population

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    End point title
    		 Milestone OS rate at 12 months in the PD-L1 CPS ≥20 population
    End point description
    OS rate at 12 months was estimated using the Kaplan-Meier method. Associated 95% confidence intervals are estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants who had a PD-L1 CPS of ≥20 are presented here.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Percentage of participants
        number (confidence interval 95%)
    46 (28 to 63)
    88 (76 to 94)
    No statistical analyses for this end point

    Secondary: Milestone OS rate at 24 months in the PD-L1 CPS ≥20 population

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    End point title
    		 Milestone OS rate at 24 months in the PD-L1 CPS ≥20 population
    End point description
    Milestone OS rate at 24 months was not evaluated. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    0 [7]
    0 [8]
    Units: Percentage of participants
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [7] - No participant had follow-up duration exceeding 24 months.
    [8] - No participant had follow-up duration exceeding 24 months.
    No statistical analyses for this end point

    Secondary: ORR per RECIST v1.1 in the PD-L1 CPS ≥1 population

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    End point title
    		 ORR per RECIST v1.1 in the PD-L1 CPS ≥1 population
    End point description
    ORR per RECIST v1.1 was defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants in the mITT population with CPS ≥1 are presented here.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Percentage of Participants
        number (confidence interval 95%)
    19.7 (13.8 to 26.8)
    25.0 (18.4 to 32.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The comparison between the treatment groups was based on the stratified Miettinen & Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    -5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.6
         upper limit
    		 4

    Secondary: ORR per RECIST v1.1 in the PD-L1 CPS ≥20 population

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    End point title
    		 ORR per RECIST v1.1 in the PD-L1 CPS ≥20 population
    End point description
    ORR per RECIST v1.1 was defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants who had a PD-L1 CPS of ≥20 are presented here.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Percentage of Participants
        number (confidence interval 95%)
    20.0 (11.4 to 31.3)
    33.3 (22.4 to 45.7)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The comparison between treatment groups was based on the stratified Miettinen & Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    -13.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.8
         upper limit
    		 1.5

    Secondary: DCR per RECIST v1.1 in the PD-L1 CPS ≥1 population

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    End point title
    		 DCR per RECIST v1.1 in the PD-L1 CPS ≥1 population
    End point description
    DCR per RECIST v1.1 based upon investigator assessment, was defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 15 weeks. A status of SD≥15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants in the mITT population with CPS ≥1 are presented here.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Percentage of Participants
        number (confidence interval 95%)
    33.1 (25.8 to 41.1)
    44.9 (36.9 to 53.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The comparison between treatment groups was based on the stratified Miettinen & Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    -11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.4
         upper limit
    		 -1.1

    Secondary: DCR per RECIST v1.1 in the PD-L1 CPS ≥20 population

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    End point title
    		 DCR per RECIST v1.1 in the PD-L1 CPS ≥20 population
    End point description
    DCR per RECIST v1.1 based upon investigator assessment, was defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 15 weeks. A status of SD≥15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants who had a PD-L1 CPS of ≥20 are presented here.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Percentage of Participants
        number (confidence interval 95%)
    37.1 (25.9 to 49.5)
    55.1 (42.6 to 67.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The comparison between treatment groups was based on the stratified Miettinen & Nurminen method with strata weighting by sample size and a single treatment covariate. Stratification factors included HPV status (positive vs. negative). Participants with oropharynx HPV negative/unknown and non-oropharyngeal tumors were combined as the HPV negative group.
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    -18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.7
         upper limit
    		 -1.4

    Secondary: Duration of response (DoR) per RECIST v1.1 in the PD-L1 CPS ≥1 population

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    End point title
    		 Duration of response (DoR) per RECIST v1.1 in the PD-L1 CPS ≥1 population
    End point description
    DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants with a best overall response of CR or PR in the mITT population with PD-L1 CPS ≥1 are presented. 99999 = The median was not reached at the time of primary completion date, the lower and upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    31
    39
    Units: Weeks
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (20.6 to 99999)
    No statistical analyses for this end point

    Secondary: DoR per RECIST v1.1 in the PD-L1 CPS ≥20 population

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    End point title
    		 DoR per RECIST v1.1 in the PD-L1 CPS ≥20 population
    End point description
    DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Data for participants with a best overall response of CR or PR in the mITT population with PD-L1 CPS ≥20 are presented. 99999 = The median was not reached at the time of primary completion date, the lower and upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    14
    23
    Units: Weeks
        median (confidence interval 95%)
    99999 (18.1 to 99999)
    99999 (12.1 to 99999)
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)

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    End point title
    		 Number of participants with any adverse events (AEs) and serious adverse events (SAEs)
    End point description
    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
        Any AE
    145
    140
        Any SAE
    46
    47
    No statistical analyses for this end point

    Secondary: Number of participants with AEs by severity

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    End point title
    		 Number of participants with AEs by severity
    End point description
    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of each AE was reported during the study and was assigned a grade according to the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE). AEs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
        Grade 1
    38
    27
        Grade 2
    47
    51
        Grade 3
    40
    43
        Grade 4
    5
    4
        Grade 5
    15
    15
    No statistical analyses for this end point

    Secondary: Number of participants with SAE by Severity

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    End point title
    		 Number of participants with SAE by Severity
    End point description
    A SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity of each SAE was reported during the study and was assigned a grade according to the NCI-CTCAE. SAEs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants experiencing SAEs of Grade ≥3 have been presented.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
        Grade ≥3
    39
    38
    No statistical analyses for this end point

    Secondary: Number of participants with AESI by severity

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    End point title
    		 Number of participants with AESI by severity
    End point description
    AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated. Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants experiencing AESIs of Grade ≥3 have been presented.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
        Grade >= 3
    1
    3
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events of special interest (AESI)

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    End point title
    		 Number of participants with adverse events of special interest (AESI)
    End point description
    AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
    41
    63
    No statistical analyses for this end point

    Secondary: Number of participants with dose modifications

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    End point title
    		 Number of participants with dose modifications
    End point description
    Number of participants with dose modifications (including dose interruptions, dose delays and treatment discontinuations) were reported by each interventional component. 99999= The number of participants with treatment discontinuation by component did not receive the mentioned study intervention
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab + pembrolizumab safety analysis set Placebo + pembrolizumab safety analysis set
    Number of subjects analysed
    159
    156
    Units: Participants
        Dose Interruption by component- feladilimab
    4
    99999
        Dose Interruption by component- placebo
    99999
    1
        Dose Interruption by component- pembrolizumab
    0
    1
        Dose delays by component- feladilimab
    9
    99999
        Dose delays by component- placebo
    99999
    5
        Dose delays by component- pembrolizumab
    11
    6
        Treatment discontinuation- feladilimab/placebo
    159
    154
        Treatment discontinuation- pembrolizumab
    108
    93
    No statistical analyses for this end point

    Secondary: Time to deterioration (TTD) in pain in the PD-L1 CPS ≥1 population

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    End point title
    		 Time to deterioration (TTD) in pain in the PD-L1 CPS ≥1 population
    End point description
    TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the European Organization for Research and Treatment of Cancer Item Library(EORTC IL51) pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC Quality of Life Questionnaire 35-Item Head and Neck Module (QLQ-H&N35) is a head and neck specific module with multi-item scales. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0–100. A high score represents a high/healthy level of functioning. Data for participants in the mITT population with CPS ≥1 are presented here. 99999 = The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Months
        median (confidence interval 95%)
    6.3 (5.1 to 99999)
    10.4 (6.3 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.783 [9]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.77
    Notes
    [9] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Secondary: TTD in pain in the PD-L1 CPS ≥20 population

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    End point title
    		 TTD in pain in the PD-L1 CPS ≥20 population
    End point description
    TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the European Organization for Research and Treatment of Cancer Item Library(EORTC IL51) pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC Quality of Life Questionnaire 35-Item Head and Neck Module (QLQ-H&N35) is a head and neck specific module with multi-item scales. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0–100. A high score represents a high/healthy level of functioning. Data for participants who had a PD-L1 CPS of ≥20 are presented here. 99999 = The median was not reached at the time of primary completion date and the upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Months
        median (confidence interval 95%)
    99999 (5.1 to 99999)
    12.0 (6.3 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5 [10]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2
    Notes
    [10] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Secondary: TTD in physical function in the PD-L1 CPS ≥1 population

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    End point title
    		 TTD in physical function in the PD-L1 CPS ≥1 population
    End point description
    TTD in physical function is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the PROMIS PF 8c. The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning. Data for participants in the mITT population with CPS ≥1 are presented here.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    157
    156
    Units: Months
        median (confidence interval 95%)
    4.9 (3.5 to 7.7)
    4.9 (3.0 to 6.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the Cox regression model with Efron's method of tie handling, a treatment covariate and stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.329 [11]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.34
    Notes
    [11] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by PD-L1 expression (CPS ≥20 vs. 1≤ CPS <20) and HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).

    Secondary: TTD in physical function in the PD-L1 CPS ≥20 population

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    End point title
    		 TTD in physical function in the PD-L1 CPS ≥20 population
    End point description
    TTD in physical function is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the PROMIS PF 8c. The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning. Data for participants who had a PD-L1 CPS of ≥20 are presented here. 99999 = The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.
    End point type
    Secondary
    End point timeframe
    Up to approximately 16 months
    End point values
    		 Feladilimab +pembrolizumab mITT analysis set Placebo + pembrolizumab mITT analysis set
    Number of subjects analysed
    70
    69
    Units: Months
        median (confidence interval 95%)
    4.9 (2.1 to 99999)
    4.9 (3.1 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The hazard ratio and 2-sided 95% CI was calculated from the cox regression model with Efron's method of tie handling, a treatment covariate and stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx).
    Comparison groups
    Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.608 [12]
    Method
    		 Stratified Cox proportional hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2
    Notes
    [12] - Nominal p-value was calculated based on the one-sided log-rank test, stratified by HPV status (oropharynx HPV positive vs oropharynx HPV negative/unknown and non-oropharynx)

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All cause mortality, non-SAEs and SAEs were collected from Day 1 to Up to approximately 16 months.
    Adverse event reporting additional description
    2 participants randomized to placebo arm, were dosed with feladilimab and included in the feladilimab arm. 1 participant randomized to feladilimab arm, never received feladilimab/placebo, was included in the placebo arm of the safety population. Safety data for participants who continue to receive Pembrolizumab will be updated after study end.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Participants receiving placebo and pembrolizumab
    Reporting group description
    		 Participants were administered placebo and pembrolizumab as an IV infusion Q3W.

    Reporting group title
    Participants receiving feladilimab and pembrolizumab
    Reporting group description
    		 Participants were administered feladilimab and pembrolizumab as an IV infusion once every Q3W.

    Serious adverse events
    		 Participants receiving placebo and pembrolizumab Participants receiving feladilimab and pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    47 / 156 (30.13%)
    46 / 159 (28.93%)
         number of deaths (all causes)
    38
    54
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected neoplasm
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tumour haemorrhage
         subjects affected / exposed
    6 / 156 (3.85%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Distributive shock
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 156 (1.28%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 156 (0.64%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Asphyxia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aspiration
         subjects affected / exposed
    0 / 156 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 156 (1.28%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 156 (1.28%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Laryngeal haemorrhage
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    4 / 156 (2.56%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    1 / 2
    Pneumonitis
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stridor
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheal haemorrhage
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheal obstruction
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Seizure
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 156 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    4 / 156 (2.56%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral cavity fistula
         subjects affected / exposed
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral pain
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Stomatitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fistula discharge
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    3 / 156 (1.92%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 156 (1.28%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 156 (1.92%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    3 / 156 (1.92%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    3 / 156 (1.92%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Participants receiving placebo and pembrolizumab Participants receiving feladilimab and pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    115 / 156 (73.72%)
    118 / 159 (74.21%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 156 (5.13%)
    8 / 159 (5.03%)
         occurrences all number
    10
    9
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 156 (1.28%)
    8 / 159 (5.03%)
         occurrences all number
    2
    9
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 156 (3.85%)
    10 / 159 (6.29%)
         occurrences all number
    8
    12
    Weight decreased
         subjects affected / exposed
    24 / 156 (15.38%)
    18 / 159 (11.32%)
         occurrences all number
    24
    18
    Nervous system disorders
    Headache
         subjects affected / exposed
    13 / 156 (8.33%)
    14 / 159 (8.81%)
         occurrences all number
    14
    17
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    20 / 156 (12.82%)
    26 / 159 (16.35%)
         occurrences all number
    24
    31
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    12 / 156 (7.69%)
    15 / 159 (9.43%)
         occurrences all number
    19
    15
    Pyrexia
         subjects affected / exposed
    8 / 156 (5.13%)
    11 / 159 (6.92%)
         occurrences all number
    9
    13
    Fatigue
         subjects affected / exposed
    23 / 156 (14.74%)
    28 / 159 (17.61%)
         occurrences all number
    25
    28
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    24 / 156 (15.38%)
    20 / 159 (12.58%)
         occurrences all number
    27
    23
    Diarrhoea
         subjects affected / exposed
    10 / 156 (6.41%)
    17 / 159 (10.69%)
         occurrences all number
    15
    20
    Dysphagia
         subjects affected / exposed
    12 / 156 (7.69%)
    17 / 159 (10.69%)
         occurrences all number
    12
    17
    Nausea
         subjects affected / exposed
    15 / 156 (9.62%)
    16 / 159 (10.06%)
         occurrences all number
    17
    19
    Vomiting
         subjects affected / exposed
    6 / 156 (3.85%)
    11 / 159 (6.92%)
         occurrences all number
    6
    14
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    8 / 156 (5.13%)
    10 / 159 (6.29%)
         occurrences all number
    8
    11
    Dyspnoea
         subjects affected / exposed
    14 / 156 (8.97%)
    15 / 159 (9.43%)
         occurrences all number
    14
    15
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    14 / 156 (8.97%)
    9 / 159 (5.66%)
         occurrences all number
    15
    10
    Rash
         subjects affected / exposed
    18 / 156 (11.54%)
    9 / 159 (5.66%)
         occurrences all number
    24
    10
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 156 (3.21%)
    14 / 159 (8.81%)
         occurrences all number
    5
    14
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    15 / 156 (9.62%)
    11 / 159 (6.92%)
         occurrences all number
    15
    11
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 156 (5.13%)
    7 / 159 (4.40%)
         occurrences all number
    8
    7
    Arthralgia
         subjects affected / exposed
    10 / 156 (6.41%)
    10 / 159 (6.29%)
         occurrences all number
    15
    10
    Neck pain
         subjects affected / exposed
    9 / 156 (5.77%)
    7 / 159 (4.40%)
         occurrences all number
    9
    7
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    7 / 156 (4.49%)
    11 / 159 (6.92%)
         occurrences all number
    8
    15
    Hypercalcaemia
         subjects affected / exposed
    7 / 156 (4.49%)
    9 / 159 (5.66%)
         occurrences all number
    9
    12
    Decreased appetite
         subjects affected / exposed
    23 / 156 (14.74%)
    15 / 159 (9.43%)
         occurrences all number
    23
    15
    Hyponatraemia
         subjects affected / exposed
    5 / 156 (3.21%)
    12 / 159 (7.55%)
         occurrences all number
    5
    17

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Oct 2019
    Amendment 1: Generated to provide additional clarification that PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay used by the central laboratories in determining PD-L1 CPS status for study eligibility was the US FDA approved and European Union (EU) CE marked PD-L1 IHC 22C3 pharmDx assay.
    19 May 2020
    Amendment 2: Generated to include eligibility criteria to restrict the population to have recurrence >6 months from completion of chemoradiation therapy, to address complications of rapid disease progression such as increased risk of tumor associated bleeding that was inherent to the underlying disease of HNSCC and additional clarification regarding unstable medical condition. Additional updates included accounting for the possibility of a non-proportional hazard effect and tail effect in the statistical plan; definition of second course of study treatment that was expanded to include participants who complete 35 cycles of study treatment.
    29 Jun 2021
    Amendment 3: Generated to update the Schedule of Activities (SoA), due to the study status in which there is no further accrual and feladilimab is no longer being administered

    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.
    Data are reported following the interim analysis decision to stop further accrual into the study and discontinue feladilimab/placebo. The study primary completion analysis results should be interpreted with consideration of the immature data
    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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