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
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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 |
20 Jun 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
04 Jul 2024
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First version publication date |
12 May 2022
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
209229
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04128696 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jul 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Jun 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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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).
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Nov 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 1
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Country: Number of subjects enrolled |
Australia: 20
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Country: Number of subjects enrolled |
Brazil: 10
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Country: Number of subjects enrolled |
Canada: 31
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Country: Number of subjects enrolled |
China: 16
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Country: Number of subjects enrolled |
Denmark: 1
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Country: Number of subjects enrolled |
France: 21
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Country: Number of subjects enrolled |
Germany: 7
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Country: Number of subjects enrolled |
Greece: 2
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Country: Number of subjects enrolled |
Israel: 1
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Country: Number of subjects enrolled |
Italy: 12
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Country: Number of subjects enrolled |
Japan: 20
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Country: Number of subjects enrolled |
Korea, Republic of: 18
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Country: Number of subjects enrolled |
Mexico: 2
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Country: Number of subjects enrolled |
Netherlands: 7
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Country: Number of subjects enrolled |
Norway: 6
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Country: Number of subjects enrolled |
Poland: 26
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Country: Number of subjects enrolled |
Portugal: 5
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Country: Number of subjects enrolled |
Romania: 29
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Country: Number of subjects enrolled |
Russian Federation: 18
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Country: Number of subjects enrolled |
Spain: 13
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Country: Number of subjects enrolled |
Switzerland: 3
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Country: Number of subjects enrolled |
Taiwan: 6
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Country: Number of subjects enrolled |
United Kingdom: 15
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Country: Number of subjects enrolled |
United States: 25
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Worldwide total number of subjects |
315
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EEA total number of subjects |
129
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
174
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From 65 to 84 years |
138
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85 years and over |
3
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Recruitment
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Recruitment details |
Total of 315 participants with recurrent or metastatic head and neck squamous cell carcinoma/cancer (HNSCC) were enrolled in this study. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Recruitment in the study was stopped following review of interim safety and efficacy data by the Independent Data Monitoring Committee, after a pre-specified futility analysis. A Dear Investigator Letter (DIL) was issued to stop screening/randomization of further subjects to the study. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants were administered feladilimab in combination with pembrolizumab as an intravenous infusion over approximately 30 minutes every Q3W.
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants were administered placebo in combination with pembrolizumab as an intravenous infusion over approximately 30 minutes every Q3W.
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Baseline characteristics reporting groups
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Reporting group title |
Participants receiving feladilimab and pembrolizumab
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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
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Reporting group description |
Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion Q3W. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Participants receiving feladilimab and pembrolizumab
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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
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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
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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.
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Subject analysis set title |
Placebo + pembrolizumab safety analysis set
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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.
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Subject analysis set title |
Feladilimab +pembrolizumab mITT analysis set
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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.
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Subject analysis set title |
Placebo + pembrolizumab mITT analysis set
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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.
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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.
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End point type |
Primary
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End point timeframe |
Up to approximately 16 months
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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).
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
313
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.973 [1] | ||||||||||||
Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.51
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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) |
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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.
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End point type |
Primary
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End point timeframe |
Up to approximately 16 months
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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)
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
139
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
> 0.999 [2] | ||||||||||||
Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
4.44
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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). |
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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.
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End point type |
Primary
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End point timeframe |
Up to approximately 16 months
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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)
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
313
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.989 [3] | ||||||||||||
Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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). |
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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.
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End point type |
Secondary
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End point timeframe |
Up to approximately 16 months
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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)
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
313
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.996 [4] | ||||||||||||
Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.48
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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). |
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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.
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End point type |
Secondary
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End point timeframe |
Up to approximately 16 months
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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)
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
139
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Analysis specification |
Pre-specified
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Analysis type |
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Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.55
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.98 | ||||||||||||
upper limit |
2.43 |
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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.
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End point type |
Secondary
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End point timeframe |
Up to approximately 16 months
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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).
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Comparison groups |
Feladilimab +pembrolizumab mITT analysis set v Placebo + pembrolizumab mITT analysis set
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Number of subjects included in analysis |
139
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Analysis specification |
Pre-specified
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Analysis type |
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Method |
Stratified Cox proportional hazard model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.59
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1 | ||||||||||||
upper limit |
2.53 |
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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.
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End point type |
Secondary
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End point timeframe |
12 months
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No statistical analyses for this end point |
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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.
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End point type |
Secondary
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End point timeframe |
24 months
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
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 43 months
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
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 43 months
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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 43 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
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 43 months
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
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
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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 43 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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). |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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). |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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). |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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 information
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Timeframe for reporting adverse events |
All cause mortality, non-SAEs and SAEs were collected from Day 1 to Up to approximately 43 months.
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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.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Participants receiving placebo and pembrolizumab
|
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Reporting group description |
Participants were administered placebo and pembrolizumab as an IV infusion Q3W. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Participants receiving feladilimab and pembrolizumab
|
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Reporting group description |
Participants were administered feladilimab and pembrolizumab as an IV infusion once every Q3W. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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. |
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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 |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |