Trial Outcomes & Findings for Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412) (NCT NCT03040999)

Last Updated: 2026-02-04

Results Overview

EFS was defined as the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery \>20 weeks from end of CRT when invasive cancer is present. The non-parametric Kaplan-Meier method was used to estimate the EFS curve in each treatment group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

804 participants

Primary outcome timeframe

Up to approximately 62 months

Results posted on

2026-02-04

Participant Flow

Participants were enrolled who had locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) and who were eligible for definitive chemoradiation therapy (CRT) and not considered for primary surgery based on investigator decision; had an Eastern Cooperative Oncology Group performance score of 0 or 1; had no distant metastases; and no active autoimmune disease or infection requiring systemic therapy.

Participant milestones

Participant milestones
Measure	Pembrolizumab + CRT + Pembrolizumab On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Overall Study STARTED	402	402
Overall Study Treated	398	398
Overall Study COMPLETED	233	213
Overall Study NOT COMPLETED	169	189

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + CRT + Pembrolizumab On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Overall Study Lost to Follow-up	2	2
Overall Study Withdrawal by Subject	12	13
Overall Study Death	155	171
Overall Study Physician Decision	0	3

Baseline Characteristics

Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + CRT + Pembrolizumab n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.	Total n=804 Participants Total of all reporting groups
Age, Continuous	58.8 Years STANDARD_DEVIATION 9.0 • n=25 Participants	58.6 Years STANDARD_DEVIATION 7.8 • n=26 Participants	58.7 Years STANDARD_DEVIATION 8.4 • n=51 Participants
Sex: Female, Male Female	71 Participants n=25 Participants	73 Participants n=26 Participants	144 Participants n=51 Participants
Sex: Female, Male Male	331 Participants n=25 Participants	329 Participants n=26 Participants	660 Participants n=51 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	47 Participants n=25 Participants	59 Participants n=26 Participants	106 Participants n=51 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	324 Participants n=25 Participants	312 Participants n=26 Participants	636 Participants n=51 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	31 Participants n=25 Participants	31 Participants n=26 Participants	62 Participants n=51 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=25 Participants	0 Participants n=26 Participants	2 Participants n=51 Participants
Race (NIH/OMB) Asian	54 Participants n=25 Participants	48 Participants n=26 Participants	102 Participants n=51 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants
Race (NIH/OMB) Black or African American	10 Participants n=25 Participants	11 Participants n=26 Participants	21 Participants n=51 Participants
Race (NIH/OMB) White	314 Participants n=25 Participants	313 Participants n=26 Participants	627 Participants n=51 Participants
Race (NIH/OMB) More than one race	19 Participants n=25 Participants	28 Participants n=26 Participants	47 Participants n=51 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=25 Participants	2 Participants n=26 Participants	5 Participants n=51 Participants
Human Papilloma Virus (HPV) Status Positive	109 Participants n=25 Participants	104 Participants n=26 Participants	213 Participants n=51 Participants
Human Papilloma Virus (HPV) Status Negative	293 Participants n=25 Participants	298 Participants n=26 Participants	591 Participants n=51 Participants
Disease stage at baseline AJCC7 III	8 Participants n=25 Participants	11 Participants n=26 Participants	19 Participants n=51 Participants
Disease stage at baseline AJCC7 IVA	61 Participants n=25 Participants	58 Participants n=26 Participants	119 Participants n=51 Participants
Disease stage at baseline AJCC7 IVB	12 Participants n=25 Participants	14 Participants n=26 Participants	26 Participants n=51 Participants
Disease stage at baseline AJCC8 II	0 Participants n=25 Participants	1 Participants n=26 Participants	1 Participants n=51 Participants
Disease stage at baseline AJCC8 III	132 Participants n=25 Participants	125 Participants n=26 Participants	257 Participants n=51 Participants
Disease stage at baseline AJCC8 IVA	146 Participants n=25 Participants	152 Participants n=26 Participants	298 Participants n=51 Participants
Disease stage at baseline AJCC8 IVB	43 Participants n=25 Participants	41 Participants n=26 Participants	84 Participants n=51 Participants

PRIMARY outcome

Timeframe: Up to approximately 62 months

Population: All randomized participants based on the treatment group to which they were randomized.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Event-free Survival (EFS)	NA Months Interval 44.7 to NA = median and upper limit not reached due to insufficient number of participants with an event.	46.6 Months Interval 27.5 to NA = upper limit not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 62 months

Population: All randomized participants based on the treatment group to which they were randomized.

OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of analysis were censored at the date the participant was last known to be alive. The non-parametric Kaplan-Meier method was used to estimate the survival curve in each treatment group.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=402 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Overall Survival (OS)	NA Months NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event.	NA Months NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 88 months

Population: All randomized participants who received at least one dose of study treatment.

An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who experienced an AE is presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=398 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=398 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Number of Participants Who Experienced an Adverse Event (AE)	398 Participants	397 Participants

SECONDARY outcome

Timeframe: Up to approximately 15 months

Population: All randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=398 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=398 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Number of Participants Who Discontinued Study Drug Due to an AE	163 Participants	132 Participants

SECONDARY outcome

Timeframe: Baseline and up to week 45

Population: Participants with at least one patient reported outcome (PRO) assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. For Global Health Status (GHS) (Item 29), participants are asked "How would you rate your overall health during the past week?" Individual items are scored on a 7-point (1=very poor to 7=excellent). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation, with a higher score indicating a better level of function and better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Analysis based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=393 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=392 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) Score	1.93 Scores on a scale Interval -0.12 to 3.99	6.17 Scores on a scale Interval 4.1 to 8.23

SECONDARY outcome

Timeframe: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=393 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=391 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Swallowing Score	-3.86 Scores on a scale Interval -6.57 to -1.15	-3.35 Scores on a scale Interval -6.08 to -0.62

SECONDARY outcome

Timeframe: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the speech scale (Items 30-32) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in speech was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=393 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=391 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Speech Score	-6.22 Scores on a scale Interval -8.89 to -3.54	-4.93 Scores on a scale Interval -7.62 to -2.23

SECONDARY outcome

Timeframe: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and Neck Cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=393 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=391 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Pain Symptom Score	-10.55 Scores on a scale Interval -12.87 to -8.22	-11.84 Scores on a scale Interval -14.18 to -9.5

SECONDARY outcome

Timeframe: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better physical functioning. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Analysis was based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Outcome measures

Outcome measures
Measure	Pembrolizumab + CRT + Pembrolizumab n=393 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	Placebo + CRT + Placebo n=392 Participants On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m\^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning Score	-5.58 Scores on a scale Interval -7.37 to -3.8	-3.53 Scores on a scale Interval -5.32 to -1.74

Adverse Events

Pembrolizumab + CRT + Pembrolizumab

Serious events: 245 serious events

Other events: 398 other events

Deaths: 156 deaths

Placebo + CRT + Placebo

Serious events: 197 serious events

Other events: 396 other events

Deaths: 178 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER