Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02252042
• Collaborator: (none)
• Enrollment: 495
• Arms: 2
• Anticipated Duration (Months): 92.9

Study Details

Study Description

Brief Summary

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Cancer	Biological: pembrolizumab; Drug: methotrexate; Drug: docetaxel; Biological: cetuximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 495 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
• Actual Study Start Date: Nov 17, 2014
• Actual Primary Completion Date: May 15, 2017
• Anticipated Study Completion Date: Aug 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembroliziumab Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle.	Biological: pembrolizumab; Other Names: MK-3475 KEYTRUDA®
Active Comparator: Active Comparator Participants receive methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.	Drug: methotrexate; Drug: docetaxel; Biological: cetuximab

Outcome Measures

Primary Outcome Measures

1. Initial Overall Survival (OS) for All Participants [Up to approximately 2 years (Database lock on 04-Jun-2017)]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.

2. Updated Final OS for All Participants [Up to approximately 2 years (Database update on 13-Oct-2017)]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

Secondary Outcome Measures

1. OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS) [Up to approximately 2 years]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants [Up to approximately 2 years]

   PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

3. PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

   PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

4. Objective Response Rate (ORR) Per RECIST 1.1 in All Participants [Up to approximately 2 years]

   ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

5. ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

   ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

6. Duration of Response (DOR) Per RECIST 1.1 in All Participants [Up to approximately 2 years]

   For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

7. DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

   For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

8. Time to Progression (TTP) Per RECIST 1.1 in All Participants [Up to approximately 2 years]

   TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

9. TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

   TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

10. PFS Per Modified RECIST in All Participants [Up to approximately 2 years]

    PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

11. PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

    PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.

12. Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants [Up to approximately 27 months]

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.

13. Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS [Up to approximately 27 months]

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.

14. Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants [Up to approximately 2 years]

    The number of all participants who discontinued study treatment due to an AE is presented.

15. Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS [Up to approximately 2 years]

    The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies

• Failure of prior platinum therapy

• Radiographically-measurable disease based on RECIST 1.1

• Tumor tissue available for PD-L1 biomarker analysis

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

• Adequate organ function

• Female participants of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care

• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care

Exclusion Criteria

• Disease is suitable for local therapy administered with curative intent

• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization

• Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease

• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy

• Not recovered from adverse events due to therapy more than 4 weeks earlier

• Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1, or not recovered from adverse events due to agents administered more than 4 weeks earlier

• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1

• Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast cancers

• Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents

• Active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Active, non-infectious pneumonitis

• Active infection requiring systemic therapy

• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial therapy according to local standard of care

• Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial

• Human immunodeficiency virus (HIV)

• Hepatitis B or C

• Live vaccine within 30 days of planned start of study therapy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 12, 2018

More Information

Additional Information:

• Merck Oncology Clinical Trials Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02252042
• Other Study ID Numbers: 3475-040; 2014-001749-26; MK-3475-040
• First Posted: Sep 29, 2014
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Sharp & Dohme LLC: Squamous cell carcinoma; Head and neck carcinoma; PD1; PD-1; PDL1; PD-L1
• Additional relevant MeSH terms: Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Docetaxel; Pembrolizumab; Methotrexate; Cetuximab

Study Results

Participant Flow

Pre-assignment Detail	This results disclosure is based on a data cutoff date of 15 May 2017, at which time 99 participants were ongoing in the study.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Period Title: Overall Study
STARTED	247	248
Treated	246	234
COMPLETED	0	0
NOT COMPLETED	247	248

Baseline Characteristics

Arm/Group Title	Pembrolizumab	Active Comparator	Total
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.	Total of all reporting groups
Overall Participants	247	248	495
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.3 (9.8)	60.2 (8.6)	60.2 (9.2)
Sex: Female, Male (Count of Participants)
Female	40 16.2%	43 17.3%	83 16.8%
Male	207 83.8%	205 82.7%	412 83.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%	0 0%	2 0.4%
Asian	15 6.1%	16 6.5%	31 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 1.2%	7 2.8%	10 2%
White	207 83.8%	207 83.5%	414 83.6%
More than one race	4 1.6%	3 1.2%	7 1.4%
Unknown or Not Reported	16 6.5%	15 6%	31 6.3%
Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS) (Count of Participants)
TPS=0%	103 41.7%	93 37.5%	196 39.6%
1%<=TPS<50%	79 32%	87 35.1%	166 33.5%
TPS >=50%	64 25.9%	65 26.2%	129 26.1%
Missing	1 0.4%	3 1.2%	4 0.8%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants)
EGOG PS=0	71 28.7%	67 27%	138 27.9%
ECOG PS=1	176 71.3%	180 72.6%	356 71.9%
ECOG PS=2	0 0%	1 0.4%	1 0.2%
Human Papillomavirus (HPV) Tumor Status (Count of Participants)
Positive HPV Status	61 24.7%	58 23.4%	119 24%
Negative HPV Status	186 75.3%	190 76.6%	376 76%
PD-L1 Combined Positive Score (CPS) Status (Count of Participants)
PD-L1 CPS <1	50 20.2%	54 21.8%	104 21%
PD-L1 CPS ≥1	196 79.4%	191 77%	387 78.2%
Missing	1 0.4%	3 1.2%	4 0.8%

Outcome Measures

1. Primary Outcome

Title	Initial Overall Survival (OS) for All Participants
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
Time Frame	Up to approximately 2 years (Database lock on 04-Jun-2017)

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Median (95% Confidence Interval) [Months]	8.4	7.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03160
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

2. Primary Outcome

Title	Updated Final OS for All Participants
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years (Database update on 13-Oct-2017)

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Median (95% Confidence Interval) [Months]	8.4	6.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01605
	Comments	Nominal p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.65 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Nominal HR. Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

3. Secondary Outcome

Title	OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	196	191
Median (95% Confidence Interval) [Months]	8.7	7.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.00493
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

4. Secondary Outcome

Title	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
Description	PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Median (95% Confidence Interval) [Months]	2.1	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32504
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

5. Secondary Outcome

Title	PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description	PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	196	191
Median (95% Confidence Interval) [Months]	2.2	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07736
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a single covariate

6. Secondary Outcome

Title	Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
Description	ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Number (95% Confidence Interval) [Percentage of Participants]	14.6 5.9%	10.1 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0610
	Comments
	Method	Log Rank
	Comments	H0: difference in %=0; H1: difference in %>0
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

7. Secondary Outcome

Title	ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description	ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	196	191
Number (95% Confidence Interval) [Percentage of Participants]	17.3 7%	9.9 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0171
	Comments
	Method	Log Rank
	Comments	H0: difference in %=0; H1: difference in %>0
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95%; 0.6 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

8. Secondary Outcome

Title	Duration of Response (DOR) Per RECIST 1.1 in All Participants
Description	For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	26	18
Median (Full Range) [Months]	18.4	5.0

9. Secondary Outcome

Title	DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description	For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	26	15
Median (Full Range) [Months]	18.4	9.6

10. Secondary Outcome

Title	Time to Progression (TTP) Per RECIST 1.1 in All Participants
Description	TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Median (95% Confidence Interval) [Months]	2.2	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14545
	Comments	p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

11. Secondary Outcome

Title	TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description	TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	196	191
Median (Full Range) [Months]	2.7	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05851
	Comments	p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

12. Secondary Outcome

Title	PFS Per Modified RECIST in All Participants
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	247	248
Median (95% Confidence Interval) [Months]	3.5	4.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.65759
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

13. Secondary Outcome

Title	PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	196	191
Median (95% Confidence Interval) [Months]	3.6	4.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Active Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51982
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)

14. Secondary Outcome

Title	Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
Description	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
Time Frame	Up to approximately 27 months

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	246	234
Count of Participants [Participants]	238 96.4%	227 91.5%

15. Secondary Outcome

Title	Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
Description	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.
Time Frame	Up to approximately 27 months

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	195	183
Count of Participants [Participants]	192 77.7%	178 71.8%

16. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
Description	The number of all participants who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	246	234
Count of Participants [Participants]	28 11.3%	37 14.9%

17. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
Description	The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.	Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Measure Participants	195	183
Count of Participants [Participants]	24 9.7%	30 12.1%

Adverse Events

Time Frame	Up to approximately 27 months (Up to 90 days after last dose of study drug)
Adverse Event Reporting Description	Safety Population: All participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as SAEs, with the exception of drug-related deaths, which are reported as "Malignant Neoplasm Progression".
Arm/Group Title	Pembrolizumab		Active Comparator
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.		Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
All Cause Mortality
	Pembrolizumab		Active Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	181/246 (73.6%)		207/234 (88.5%)
Serious Adverse Events
	Pembrolizumab		Active Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/246 (44.7%)		92/234 (39.3%)
Blood and lymphatic system disorders
Anaemia	5/246 (2%)	5	2/234 (0.9%)	2
Anaemia of malignant disease	1/246 (0.4%)	3	0/234 (0%)	0
Febrile neutropenia	0/246 (0%)	0	9/234 (3.8%)	9
Lymph node haemorrhage	0/246 (0%)	0	1/234 (0.4%)	1
Pancytopenia	0/246 (0%)	0	1/234 (0.4%)	1
Cardiac disorders
Myocardial infarction	0/246 (0%)	0	1/234 (0.4%)	1
Pericardial effusion	1/246 (0.4%)	1	0/234 (0%)	0
Endocrine disorders
Hypercalcaemia of malignancy	3/246 (1.2%)	3	2/234 (0.9%)	2
Gastrointestinal disorders
Abdominal pain upper	0/246 (0%)	0	1/234 (0.4%)	1
Colitis	2/246 (0.8%)	2	1/234 (0.4%)	1
Constipation	0/246 (0%)	0	1/234 (0.4%)	1
Diarrhoea	6/246 (2.4%)	8	2/234 (0.9%)	2
Dysphagia	4/246 (1.6%)	4	3/234 (1.3%)	3
Gastrointestinal haemorrhage	0/246 (0%)	0	2/234 (0.9%)	2
Gastrointestinal inflammation	0/246 (0%)	0	1/234 (0.4%)	1
Incarcerated inguinal hernia	0/246 (0%)	0	1/234 (0.4%)	1
Inguinal hernia	1/246 (0.4%)	1	0/234 (0%)	0
Large intestine perforation	1/246 (0.4%)	1	0/234 (0%)	0
Malignant dysphagia	0/246 (0%)	0	1/234 (0.4%)	1
Mouth haemorrhage	3/246 (1.2%)	3	3/234 (1.3%)	3
Nausea	0/246 (0%)	0	1/234 (0.4%)	1
Oral discharge	0/246 (0%)	0	1/234 (0.4%)	1
Pneumoperitoneum	0/246 (0%)	0	1/234 (0.4%)	1
Stomatitis	1/246 (0.4%)	1	3/234 (1.3%)	3
Upper gastrointestinal haemorrhage	0/246 (0%)	0	1/234 (0.4%)	1
General disorders
Asthenia	1/246 (0.4%)	1	0/234 (0%)	0
Death	5/246 (2%)	5	4/234 (1.7%)	4
Euthanasia	0/246 (0%)	0	1/234 (0.4%)	1
Face oedema	1/246 (0.4%)	1	1/234 (0.4%)	1
General physical health deterioration	0/246 (0%)	0	1/234 (0.4%)	1
Ill-defined disorder	0/246 (0%)	0	1/234 (0.4%)	1
Malaise	1/246 (0.4%)	1	2/234 (0.9%)	2
Performance status decreased	0/246 (0%)	0	1/234 (0.4%)	1
Pyrexia	1/246 (0.4%)	1	3/234 (1.3%)	3
Hepatobiliary disorders
Autoimmune hepatitis	1/246 (0.4%)	1	0/234 (0%)	0
Cholelithiasis	1/246 (0.4%)	1	0/234 (0%)	0
Cirrhosis alcoholic	0/246 (0%)	0	1/234 (0.4%)	1
Immune system disorders
Anaphylactic reaction	1/246 (0.4%)	1	1/234 (0.4%)	1
Hypersensitivity	1/246 (0.4%)	1	0/234 (0%)	0
Infections and infestations
Bronchitis	1/246 (0.4%)	1	1/234 (0.4%)	1
Candida sepsis	1/246 (0.4%)	1	0/234 (0%)	0
Cellulitis	3/246 (1.2%)	4	0/234 (0%)	0
Clostridium difficile colitis	0/246 (0%)	0	2/234 (0.9%)	2
Colonic abscess	0/246 (0%)	0	1/234 (0.4%)	1
Disseminated tuberculosis	0/246 (0%)	0	1/234 (0.4%)	1
Epiglottitis	0/246 (0%)	0	1/234 (0.4%)	1
Herpes zoster	0/246 (0%)	0	1/234 (0.4%)	1
Infected fistula	0/246 (0%)	0	1/234 (0.4%)	1
Infection	0/246 (0%)	0	1/234 (0.4%)	1
Infective exacerbation of chronic obstructive airways disease	1/246 (0.4%)	2	0/234 (0%)	0
Influenza	1/246 (0.4%)	1	1/234 (0.4%)	1
Klebsiella infection	1/246 (0.4%)	1	0/234 (0%)	0
Lower respiratory tract infection	0/246 (0%)	0	1/234 (0.4%)	1
Lower respiratory tract infection bacterial	2/246 (0.8%)	2	0/234 (0%)	0
Lung infection	1/246 (0.4%)	1	2/234 (0.9%)	3
Neutropenic sepsis	0/246 (0%)	0	1/234 (0.4%)	1
Oral bacterial infection	1/246 (0.4%)	1	0/234 (0%)	0
Oral candidiasis	0/246 (0%)	0	2/234 (0.9%)	2
Pneumocystis jirovecii pneumonia	0/246 (0%)	0	1/234 (0.4%)	1
Pneumonia	20/246 (8.1%)	21	16/234 (6.8%)	17
Pulmonary sepsis	1/246 (0.4%)	1	0/234 (0%)	0
Respiratory tract infection	0/246 (0%)	0	1/234 (0.4%)	1
Sepsis	4/246 (1.6%)	4	3/234 (1.3%)	3
Septic shock	0/246 (0%)	0	1/234 (0.4%)	1
Stoma site infection	0/246 (0%)	0	1/234 (0.4%)	1
Subcutaneous abscess	1/246 (0.4%)	1	0/234 (0%)	0
Upper respiratory tract infection	1/246 (0.4%)	1	0/234 (0%)	0
Urinary tract infection	1/246 (0.4%)	1	2/234 (0.9%)	2
Urosepsis	2/246 (0.8%)	2	0/234 (0%)	0
Wound infection	0/246 (0%)	0	1/234 (0.4%)	1
Injury, poisoning and procedural complications
Accidental overdose	1/246 (0.4%)	1	1/234 (0.4%)	1
Alcohol poisoning	1/246 (0.4%)	1	0/234 (0%)	0
Fall	1/246 (0.4%)	1	0/234 (0%)	0
Femoral neck fracture	1/246 (0.4%)	1	0/234 (0%)	0
Hip fracture	1/246 (0.4%)	1	0/234 (0%)	0
Postoperative fever	1/246 (0.4%)	1	0/234 (0%)	0
Procedural hypotension	1/246 (0.4%)	1	0/234 (0%)	0
Spinal fracture	0/246 (0%)	0	1/234 (0.4%)	1
Stoma site haemorrhage	0/246 (0%)	0	1/234 (0.4%)	2
Stoma site ulcer	1/246 (0.4%)	1	0/234 (0%)	0
Subarachnoid haemorrhage	0/246 (0%)	0	1/234 (0.4%)	1
Tracheostomy malfunction	1/246 (0.4%)	1	1/234 (0.4%)	1
Investigations
Blood creatinine increased	1/246 (0.4%)	1	0/234 (0%)	0
Hepatic enzyme increased	0/246 (0%)	0	1/234 (0.4%)	1
Neutrophil count decreased	0/246 (0%)	0	3/234 (1.3%)	5
Platelet count decreased	0/246 (0%)	0	1/234 (0.4%)	1
Weight decreased	1/246 (0.4%)	1	0/234 (0%)	0
White blood cell count decreased	0/246 (0%)	0	2/234 (0.9%)	2
Metabolism and nutrition disorders
Decreased appetite	4/246 (1.6%)	4	0/234 (0%)	0
Dehydration	2/246 (0.8%)	2	3/234 (1.3%)	3
Diabetes mellitus inadequate control	0/246 (0%)	0	1/234 (0.4%)	1
Hypercalcaemia	7/246 (2.8%)	7	0/234 (0%)	0
Hyponatraemia	3/246 (1.2%)	3	0/234 (0%)	0
Musculoskeletal and connective tissue disorders
Kyphosis	1/246 (0.4%)	1	0/234 (0%)	0
Muscular weakness	1/246 (0.4%)	1	0/234 (0%)	0
Soft tissue haemorrhage	1/246 (0.4%)	1	0/234 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade	1/246 (0.4%)	1	0/234 (0%)	0
Basal cell carcinoma	0/246 (0%)	0	1/234 (0.4%)	1
Colon cancer	1/246 (0.4%)	1	0/234 (0%)	0
Infected neoplasm	2/246 (0.8%)	2	0/234 (0%)	0
Malignant neoplasm progression	1/246 (0.4%)	1	1/234 (0.4%)	1
Paraneoplastic syndrome	1/246 (0.4%)	1	0/234 (0%)	0
Rectal cancer	1/246 (0.4%)	1	0/234 (0%)	0
Tumour haemorrhage	9/246 (3.7%)	10	2/234 (0.9%)	4
Tumour pain	0/246 (0%)	0	2/234 (0.9%)	2
Nervous system disorders
Cerebrovascular accident	1/246 (0.4%)	1	0/234 (0%)	0
Guillain-Barre syndrome	1/246 (0.4%)	1	0/234 (0%)	0
Seizure	0/246 (0%)	0	1/234 (0.4%)	1
Somnolence	1/246 (0.4%)	1	0/234 (0%)	0
Spinal cord compression	2/246 (0.8%)	3	0/234 (0%)	0
Syncope	1/246 (0.4%)	1	0/234 (0%)	0
Vocal cord paresis	0/246 (0%)	0	1/234 (0.4%)	1
Psychiatric disorders
Confusional state	1/246 (0.4%)	1	1/234 (0.4%)	1
Delirium	0/246 (0%)	0	1/234 (0.4%)	1
Renal and urinary disorders
Acute kidney injury	1/246 (0.4%)	1	0/234 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/246 (0.4%)	1	1/234 (0.4%)	1
Asphyxia	0/246 (0%)	0	1/234 (0.4%)	1
Aspiration	0/246 (0%)	0	1/234 (0.4%)	1
Chronic obstructive pulmonary disease	1/246 (0.4%)	2	1/234 (0.4%)	3
Dyspnoea	4/246 (1.6%)	4	1/234 (0.4%)	1
Eosinophilic pneumonia	1/246 (0.4%)	1	0/234 (0%)	0
Epistaxis	1/246 (0.4%)	1	0/234 (0%)	0
Haemoptysis	2/246 (0.8%)	3	0/234 (0%)	0
Hypoxia	1/246 (0.4%)	1	0/234 (0%)	0
Laryngeal obstruction	1/246 (0.4%)	1	0/234 (0%)	0
Laryngeal stenosis	1/246 (0.4%)	1	0/234 (0%)	0
Lung disorder	0/246 (0%)	0	1/234 (0.4%)	1
Pharyngeal fistula	0/246 (0%)	0	1/234 (0.4%)	1
Pleural effusion	2/246 (0.8%)	2	0/234 (0%)	0
Pneumonia aspiration	6/246 (2.4%)	7	3/234 (1.3%)	3
Pneumonitis	6/246 (2.4%)	6	3/234 (1.3%)	3
Pneumothorax	0/246 (0%)	0	2/234 (0.9%)	2
Pulmonary embolism	0/246 (0%)	0	1/234 (0.4%)	1
Respiratory disorder	0/246 (0%)	0	1/234 (0.4%)	2
Respiratory failure	2/246 (0.8%)	2	0/234 (0%)	0
Respiratory tract haemorrhage	0/246 (0%)	0	1/234 (0.4%)	1
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis	1/246 (0.4%)	1	0/234 (0%)	0
Fungating wound	1/246 (0.4%)	1	0/234 (0%)	0
Pruritus	0/246 (0%)	0	1/234 (0.4%)	1
Skin ulcer	1/246 (0.4%)	1	0/234 (0%)	0
Stevens-Johnson syndrome	1/246 (0.4%)	1	0/234 (0%)	0
Vascular disorders
Angiodysplasia	1/246 (0.4%)	1	0/234 (0%)	0
Deep vein thrombosis	1/246 (0.4%)	1	0/234 (0%)	0
Haemorrhage	2/246 (0.8%)	2	0/234 (0%)	0
Jugular vein thrombosis	0/246 (0%)	0	1/234 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab		Active Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	212/246 (86.2%)		210/234 (89.7%)
Blood and lymphatic system disorders
Anaemia	62/246 (25.2%)	77	51/234 (21.8%)	70
Endocrine disorders
Hypothyroidism	37/246 (15%)	40	9/234 (3.8%)	9
Gastrointestinal disorders
Abdominal pain	9/246 (3.7%)	9	12/234 (5.1%)	12
Constipation	43/246 (17.5%)	49	37/234 (15.8%)	43
Diarrhoea	36/246 (14.6%)	54	41/234 (17.5%)	50
Dry mouth	15/246 (6.1%)	15	6/234 (2.6%)	6
Dysphagia	21/246 (8.5%)	23	15/234 (6.4%)	16
Nausea	34/246 (13.8%)	43	44/234 (18.8%)	52
Stomatitis	7/246 (2.8%)	9	26/234 (11.1%)	34
Vomiting	23/246 (9.3%)	27	23/234 (9.8%)	34
General disorders
Asthenia	37/246 (15%)	47	41/234 (17.5%)	52
Fatigue	48/246 (19.5%)	51	63/234 (26.9%)	81
Mucosal inflammation	17/246 (6.9%)	21	36/234 (15.4%)	51
Pyrexia	24/246 (9.8%)	38	25/234 (10.7%)	35
Investigations
Aspartate aminotransferase increased	10/246 (4.1%)	10	13/234 (5.6%)	18
Neutrophil count decreased	4/246 (1.6%)	11	24/234 (10.3%)	29
Platelet count decreased	7/246 (2.8%)	7	13/234 (5.6%)	19
Weight decreased	21/246 (8.5%)	22	26/234 (11.1%)	26
White blood cell count decreased	2/246 (0.8%)	3	12/234 (5.1%)	15
Metabolism and nutrition disorders
Decreased appetite	31/246 (12.6%)	37	43/234 (18.4%)	48
Hypercalcaemia	14/246 (5.7%)	16	13/234 (5.6%)	14
Hypokalaemia	23/246 (9.3%)	27	19/234 (8.1%)	21
Hypomagnesaemia	10/246 (4.1%)	11	20/234 (8.5%)	25
Hyponatraemia	12/246 (4.9%)	14	16/234 (6.8%)	17
Hypophosphataemia	15/246 (6.1%)	21	12/234 (5.1%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	19/246 (7.7%)	20	5/234 (2.1%)	6
Back pain	23/246 (9.3%)	24	8/234 (3.4%)	8
Neck pain	19/246 (7.7%)	19	17/234 (7.3%)	17
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	13/246 (5.3%)	13	7/234 (3%)	8
Nervous system disorders
Headache	21/246 (8.5%)	25	22/234 (9.4%)	24
Psychiatric disorders
Anxiety	13/246 (5.3%)	13	6/234 (2.6%)	6
Insomnia	22/246 (8.9%)	22	17/234 (7.3%)	17
Respiratory, thoracic and mediastinal disorders
Cough	42/246 (17.1%)	47	36/234 (15.4%)	39
Dyspnoea	30/246 (12.2%)	32	26/234 (11.1%)	31
Haemoptysis	13/246 (5.3%)	15	6/234 (2.6%)	8
Productive cough	14/246 (5.7%)	14	5/234 (2.1%)	7
Skin and subcutaneous tissue disorders
Alopecia	1/246 (0.4%)	1	27/234 (11.5%)	27
Dermatitis acneiform	0/246 (0%)	0	18/234 (7.7%)	28
Dry skin	4/246 (1.6%)	4	17/234 (7.3%)	19
Pruritus	18/246 (7.3%)	22	17/234 (7.3%)	40
Rash	25/246 (10.2%)	32	38/234 (16.2%)	81
Vascular disorders
Hypotension	12/246 (4.9%)	12	12/234 (5.1%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.