Trial · NCT03040999
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)
NCT03040999, Phase 3, Completed, Merck Sharp & Dohme LLC; results first posted 2023-06-08
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. 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). Trials, record NCT03040999. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03040999
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- 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 number
- NCT03040999
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 804 participants, actual
- Lead sponsor
- Merck Sharp & Dohme LLC
- Conditions
- Head and Neck Neoplasms
- Interventions
- Pembrolizumab, Placebo, Cisplatin, Accelerated Fractionation (AFX) Radiotherapy, Standard Fractionation (SFX) Radiotherapy
- First posted
- 2017-02-02
- Last updated
- 2026-02-04
- Other registries' IDs
- eudract:2016-003934-25
- Results first posted
- 2023-06-08
Source ClinicalTrials.gov
Registered outcomes9
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Event-free Survival (EFS) | Up to approximately 62 months | 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. |
| Secondary | Overall Survival (OS) | Up to approximately 62 months | 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. |
| Secondary | Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 88 months | 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. |
| Secondary | Number of Participants Who Discontinued Study Drug Due to an AE | Up to approximately 15 months | 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 discontinued study drug due to an AE is presented. |
| Secondary | 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 | Baseline and up to week 45 | 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. |
| Secondary | 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 | Baseline and up to Week 45 | 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. |
| Secondary | 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 | Baseline and up to Week 45 | 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. |
| Secondary | 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 | Baseline and up to Week 45 | 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. |
| Secondary | 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 | Baseline and up to Week 45 | 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. |
Source ClinicalTrials.gov
Outcomes9
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| SECONDARY | Overall Survival (OS) | Up to approximately 62 months | All randomized participants based on the treatment group to which they were randomized. | Months | MEDIAN |
| SECONDARY | Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 88 months | All randomized participants who received at least one dose of study treatment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants Who Discontinued Study Drug Due to an AE | Up to approximately 15 months | All randomized participants who received at least one dose of study treatment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | 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 | Baseline and up to week 45 | 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. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline and up to Week 45 | Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline and up to Week 45 | Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline and up to Week 45 | Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention. | Scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline and up to Week 45 | Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention. | Scores on a scale | LEAST_SQUARES_MEAN |
| PRIMARY | Event-free Survival (EFS) | Up to approximately 62 months | All randomized participants based on the treatment group to which they were randomized. | Months | MEDIAN |
Source ClinicalTrials.gov
Results by group18
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Overall Survival (OS) | Pembrolizumab + CRT + Pembrolizumab | NA | 95% Confidence Interval NA to NA | Months | |
| Overall Survival (OS) | Placebo + CRT + Placebo | NA | 95% Confidence Interval NA to NA | Months | |
| Number of Participants Who Experienced an Adverse Event (AE) | Pembrolizumab + CRT + Pembrolizumab | 398 | Participants | ||
| Number of Participants Who Experienced an Adverse Event (AE) | Placebo + CRT + Placebo | 397 | Participants | ||
| Number of Participants Who Discontinued Study Drug Due to an AE | Pembrolizumab + CRT + Pembrolizumab | 163 | Participants | ||
| Number of Participants Who Discontinued Study Drug Due to an AE | Placebo + CRT + Placebo | 132 | Participants | ||
| 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 | Pembrolizumab + CRT + Pembrolizumab | 1.93 | 95% Confidence Interval -0.12 to 3.99 | Scores on a scale | |
| 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 | Placebo + CRT + Placebo | 6.17 | 95% Confidence Interval 4.10 to 8.23 | Scores on a scale | |
| 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 | Pembrolizumab + CRT + Pembrolizumab | -3.86 | 95% Confidence Interval -6.57 to -1.15 | Scores on a scale | |
| 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 | Placebo + CRT + Placebo | -3.35 | 95% Confidence Interval -6.08 to -0.62 | Scores on a scale |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Pembrolizumab + CRT + Pembrolizumab | 402 | |
| Overall Study | STARTED | Placebo + CRT + Placebo | 402 | |
| Overall Study | Treated | Pembrolizumab + CRT + Pembrolizumab | 398 | |
| Overall Study | Treated | Placebo + CRT + Placebo | 398 | |
| Overall Study | COMPLETED | Pembrolizumab + CRT + Pembrolizumab | 233 | |
| Overall Study | COMPLETED | Placebo + CRT + Placebo | 213 | |
| Overall Study | NOT COMPLETED | Pembrolizumab + CRT + Pembrolizumab | 169 | |
| Overall Study | NOT COMPLETED | Placebo + CRT + Placebo | 189 |
Source ClinicalTrials.gov
Adverse events724
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Pembrolizumab + CRT + Pembrolizumab | 229 | 398 | 298 |
| other | Anaemia | Blood and lymphatic system disorders | Placebo + CRT + Placebo | 205 | 398 | 287 |
| other | Ear pain | Ear and labyrinth disorders | Pembrolizumab + CRT + Pembrolizumab | 28 | 398 | 29 |
| other | Ear pain | Ear and labyrinth disorders | Placebo + CRT + Placebo | 33 | 398 | 35 |
| other | Hypoacusis | Ear and labyrinth disorders | Pembrolizumab + CRT + Pembrolizumab | 80 | 398 | 84 |
| other | Hypoacusis | Ear and labyrinth disorders | Placebo + CRT + Placebo | 49 | 398 | 51 |
| other | Tinnitus | Ear and labyrinth disorders | Pembrolizumab + CRT + Pembrolizumab | 75 | 398 | 83 |
| other | Tinnitus | Ear and labyrinth disorders | Placebo + CRT + Placebo | 88 | 398 | 92 |
| other | Hyperthyroidism | Endocrine disorders | Pembrolizumab + CRT + Pembrolizumab | 40 | 398 | 43 |
| other | Hyperthyroidism | Endocrine disorders | Placebo + CRT + Placebo | 33 | 398 | 35 |
1 to 10 of 724Source ClinicalTrials.gov
See all 724 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Pembrolizumab + CRT + Pembrolizumab | 156 | 402 |
| Total, all-cause mortality | Placebo + CRT + Placebo | 178 | 402 |
| Total, other adverse events | Pembrolizumab + CRT + Pembrolizumab | 398 | 398 |
| Total, other adverse events | Placebo + CRT + Placebo | 396 | 398 |
| Total, serious adverse events | Pembrolizumab + CRT + Pembrolizumab | 245 | 398 |
| Total, serious adverse events | Placebo + CRT + Placebo | 197 | 398 |
Source ClinicalTrials.gov
Papers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons4
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Pembrolizumab + CRT + Pembrolizumab vs Placebo + CRT + Placebo: Number of Participants Who Discontinued Study Drug Due to an AE | Trial comparisons |
| Pembrolizumab + CRT + Pembrolizumab vs Placebo + CRT + Placebo: deaths from any cause | Trial comparisons |
| Pembrolizumab + CRT + Pembrolizumab vs Placebo + CRT + Placebo: Number of Participants Who Experienced an Adverse Event (AE) | Trial comparisons |
| Pembrolizumab + CRT + Pembrolizumab vs Placebo + CRT + Placebo: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03040999
GET https://conductscience.org/api/trials/v1/NCT03040999/events?page=2