Recurrent Head and Neck CancerPhase 3NCT02358031

A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048)

A Phase 3 study testing Pembrolizumab, Cisplatin and Carboplatin in people with Recurrent Head and Neck Cancer and Metastatic Head and Neck Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer
What is being tested?: Pembrolizumab, Cisplatin and Carboplatin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 882 participants
Where: No sites listed yet
Study dates: 19 Mar 2015to 19 Jul 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically- or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma considered incurable by local therapies
No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)
Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology)
Measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ function

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Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.
Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
Female participants of childbearing potential should have a negative pregnancy test and must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication
Male participants must agree to use an adequate method of contraception starting with the first dose of study medication through 180 days after the last dose of study medication

Who cannot join

Disease suitable for local therapy administered with curative intent
Has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
Radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from adverse events due to a previously administered treatment
Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of study medication
Life expectancy of <3 months and/or has rapidly progressing 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 medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor)

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Diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
Has had an allogeneic tissue/solid organ transplant
Active central nervous system metastases and/or carcinomatous meningitis
Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment
History of (non-infectious) pneumonitis that required steroids or current pneumonitis
Active infection requiring systemic therapy
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study medication
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously participated in Merck MK-3475 clinical trial
Known history of human immunodeficiency virus (HIV)
Known active Hepatitis B or C
Received a live vaccine within 30 days of planned start of study medication

About this study

Official title: A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Participants with recurrent or metastatic (R/M) squamous cell cancer of the head and neck (HNSCC) will be randomly assigned to receive pembrolizumab monotherapy [pembro mono], pembrolizumab plus chemotherapy with a platinum-based drug (cisplatin or carboplatin) and 5-Fluorouracil (5-FU) [pembro combo], or cetuximab plus a platinum-based drug (cisplatin or carboplatin) and 5-FU [control]. The overall primary study hypotheses are as follows in all participants and in participants with Programmed Cell Death Ligand 1 (PD-L1) positive expression defined by Combined Positive Score (CPS) ≥1 and CPS ≥20: 1) pembrolizumab monotherapy prolongs progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by Blinded Independent Central Review (BICR) and prolongs overall survival (OS) compared to standard treatment, and 2) pembrolizumab combination with chemotherapy prolongs PFS per RECIST 1.1 assessed by BICR and prolongs OS compared to standard treatment.

Read the detailed description

The 12 primary superiority hypotheses will be evaluated by comparing the pembro mono arm or pembro combo arm separately to the control arm, for PFS and OS in all first line (1L) R/M HNSCC participants and in 1L R/M HNSCC participants with positive PD-L1 expression (PD-L1 CPS ≥1 and CPS ≥20).

Per protocol, response/progression or adverse events (AEs) that occur during the second pembrolizumab course will not be counted towards efficacy outcome measures or safety outcome measures, respectively.

Conditions: Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer
Being tested: Pembrolizumab, Cisplatin, Carboplatin, 5-FU, Cetuximab
Keywords: Programmed Cell Death-1 (PD1, PD-1),, Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), chemotherapy, 5-fluorouracil, cisplatin, carboplatin
Medical subject headings: Head and Neck Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PembrolizumabBiological
Also called KEYTRUDA®, MK-3475
Pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years).
CisplatinDrug
Cisplatin 100 mg/m^2 IV on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]).
CarboplatinDrug
Carboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]).
5-FUDrug
5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]).
CetuximabBiological
Cetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity

Study groups in NCT02358031
Study group	Role	What they receive
Pembrolizumab Monotherapy (Pembro Mono)	Experimental	Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years). Receives: Biological: Pembrolizumab
Pembrolizumab + Chemotherapy (Pembro Combo)	Experimental	Participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years); plus cisplatin 100 mg/m^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]). Receives: Biological: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-FU
Cetuximab + Chemotherapy (Control)	Active comparator	Participants receive cetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity; plus cisplatin 100 mg/m^2 IV or carboplatin AUC 5 IV (Investigator's choice) on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months] for platinum-based therapy); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]). Receives: Drug: Cisplatin; Drug: Carboplatin; Drug: 5-FU; Biological: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: Overall Survival (OS) in All Participants
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: OS in All Participants
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months

Secondary outcomes (28)

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 12
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 12
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Month 12
Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Up to approximately 47 months
Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro combo arm and the control arm as a pre-specified secondary analysis. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Measured: Baseline, Week 15
Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)
EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and TTD in GHS/QoL combined score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Measured: Baseline up to approximately 12 months
Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)
EORTC QLQ-H\&N35 is a 35-item questionnaire to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, 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. TTD in EORTC QLQ-H\&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H\&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H\&N35 Pain Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Measured: Baseline up to approximately 12 months
Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)
EORTC QLQ-H\&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, 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; a higher score indicating more problems. TTD in EORTC QLQ-H\&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H\&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro mono arm and control arm and is presented later in the record.
Measured: Baseline up to approximately 12 months
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 12
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 12
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here, for the first course of treatment, out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Month 12
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR, for the first course of treatment, for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Up to approximately 47 months
Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score, for the first course of treatment, was compared between all participants of the pembro mono arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Measured: Baseline, Week 15
Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
EORTC-QLQ-C30 is a 30-item questionnaire to assess the QoL of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Measured: Baseline up to approximately 12 months
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score
EORTC QLQ-H\&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, 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; a higher score indicating more problems. TTD in EORTC QLQ-H\&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H\&N35 Pain Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H\&N35 Pain Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Measured: Baseline up to approximately 12 months
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score
EORTC QLQ-H\&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, 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; a higher score indicating more problems. TTD in EORTC QLQ-H\&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H\&N35 Swallowing Score, for the first course of treatment, was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis; and compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record.
Measured: Baseline up to approximately 12 months
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE, for the first course of treatment, was reported for each arm.
Measured: Up to approximately 47 months
Number of Participants Who Discontinued Study Drug Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued study drug due to an AE, for the first course of treatment, was reported for each arm.
Measured: Up to approximately 47 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Mar 201519 Jul 2023

First posted6 Feb 2015 (estimated)
Study start19 Mar 2015
Primary completion25 Feb 2019
Study completion19 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Recurrent Head and Neck CancerStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 882 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02358031
Sponsor's protocol ID: 3475-048
Other IDs: MK-3475-048, KEYNOTE-048, 2014-003698-41, 2014
Status last verified: Jul 2025
First submitted: 3 Feb 2015
Last updated: 18 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Tahara M, Greil R, Rischin D, Harrington KJ, Burtness B, de Castro G, Psyrri A, Brana I, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak WZW, Lin J, Gumuscu B, Lerman N, Soulieres D. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study. Eur J Cancer. 2025 May 15;221:115395. doi: 10.1016/j.ejca.2025.115395. Epub 2025 Apr 4.
PubMed 40262400
Oridate N, Takahashi S, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K, Yokota T, Yamazaki T, Takahashi M, Ueda T, Hanai N, Yamaguchi H, Hara H, Yoshizaki T, Yasumatsu R, Nakayama M, Shiga K, Fujii T, Mitsugi K, Takahashi K, Nohata N, Gumuscu B, Lerman N, Tahara M. First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE-048. Int J Clin Oncol. 2024 Dec;29(12):1825-1839. doi: 10.1007/s10147-024-02632-x. Epub 2024 Oct 9.
PubMed 39382718
Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
PubMed 37699333
Takahashi S, Oridate N, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K, Yokota T, Yamazaki T, Takahashi M, Ueda T, Hanai N, Yamaguchi H, Hara H, Yoshizaki T, Yasumatsu R, Nakayama M, Shiga K, Fujii T, Mitsugi K, Takahashi K, Nohata N, Gumuscu B, Swaby RF, Tahara M. First-line pembrolizumab +/- chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048. Int J Clin Oncol. 2022 Dec;27(12):1805-1817. doi: 10.1007/s10147-022-02233-6. Epub 2022 Oct 20.
PubMed 36264378
Harrington KJ, Burtness B, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11.
PubMed 36219809
Rischin D, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak WZW, Hong RL, Mendoza RG, Jia L, Chirovsky D, Norquist J, Jin F, Burtness B. Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048. Oral Oncol. 2022 May;128:105815. doi: 10.1016/j.oraloncology.2022.105815. Epub 2022 Apr 2.
PubMed 35381576
Burtness B, Rischin D, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Ge J, Swaby RF, Gumuscu B, Harrington K. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. J Clin Oncol. 2022 Jul 20;40(21):2321-2332. doi: 10.1200/JCO.21.02198. Epub 2022 Mar 25.
PubMed 35333599
Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
PubMed 31679945

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Questions to ask the study team

What is the study trying to find out?
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What happens when the study ends?

Official record

RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer
Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma

All Recurrent Head and Neck Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
ClinicalTrials.gov ID: NCT02358031
Acronym / sponsor ID: 3475-048
Conditions: Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1),, Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), chemotherapy, 5-fluorouracil, cisplatin, carboplatin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 882 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 19 Mar 2015 (actual)
Primary completion: 25 Feb 2019 (actual)
Study completion: 19 Jul 2023 (actual)
First posted: 6 Feb 2015 (estimated)
Results: Posted 17 Feb 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Pembrolizumab Monotherapy (Pembro Mono)	Experimental	Biological: PembrolizumabParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years).
Pembrolizumab + Chemotherapy (Pembro Combo)	Experimental	Biological: Pembrolizumab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FUParticipants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years); plus cisplatin 100 mg/m^2 IV or carboplatin at a target area under the curve of 5 (AUC 5) IV, per Investigator's choice, on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]).
Cetuximab + Chemotherapy (Control)	Active comparator	Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FU, Biological: CetuximabParticipants receive cetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity; plus cisplatin 100 mg/m^2 IV or carboplatin AUC 5 IV (Investigator's choice) on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months] for platinum-based therapy); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Histologically- or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma considered incurable by local therapies
No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)
Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology)
Measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key exclusion criteria (18 listed)

Disease suitable for local therapy administered with curative intent
Has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
Radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from adverse events due to a previously administered treatment
Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of study medication
Life expectancy of <3 months and/or has rapidly progressing disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PembrolizumabAlso: KEYTRUDA®, MK-3475Pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 35 cycles (up to ~2 years).	Biological	Pembrolizumab + Chemotherapy (Pembro Combo), Pembrolizumab Monotherapy (Pembro Mono)
CisplatinCisplatin 100 mg/m^2 IV on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]).	Drug	Cetuximab + Chemotherapy (Control), Pembrolizumab + Chemotherapy (Pembro Combo)
CarboplatinCarboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum [up to ~4 months]).	Drug	Cetuximab + Chemotherapy (Control), Pembrolizumab + Chemotherapy (Pembro Combo)
5-FU5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum [up to ~4 months]).	Drug	Cetuximab + Chemotherapy (Control), Pembrolizumab + Chemotherapy (Pembro Combo)
CetuximabCetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity	Biological	Cetuximab + Chemotherapy (Control)

Primary outcome

Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Combo vs Control: Overall Survival (OS) in All Participants
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record.
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, 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 had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.
Pembro Mono vs Control: OS in All Participants
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record.
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record.
Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
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 censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for the first course of treatment, for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record.

28 secondary outcomes

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
Time frame: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
Time frame: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
Time frame: Month 6
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
Time frame: Month 12
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
Time frame: Month 12
Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
Time frame: Month 12
Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants
Time frame: Up to approximately 47 months
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
Time frame: Up to approximately 47 months
Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Time frame: Baseline, Week 15
Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)
Time frame: Baseline up to approximately 12 months
Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)
Time frame: Baseline up to approximately 12 months
Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)
Time frame: Baseline up to approximately 12 months
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
Time frame: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
Time frame: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
Time frame: Month 6
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
Time frame: Month 12
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
Time frame: Month 12
Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
Time frame: Month 12
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants
Time frame: Up to approximately 47 months
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
Time frame: Up to approximately 47 months
Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
Time frame: Up to approximately 47 months
Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Time frame: Baseline, Week 15
Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Time frame: Baseline up to approximately 12 months
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score
Time frame: Baseline up to approximately 12 months
Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score
Time frame: Baseline up to approximately 12 months
Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to approximately 47 months
Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to approximately 47 months

Results and safety

Results posted to the registry on 17 Feb 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pembrolizumab Monotherapy (Pembro Mono)	301	2
Pembrolizumab + Chemotherapy (Pembro Combo)	281	1
Cetuximab + Chemotherapy (Control)	300	0

Primary outcome: Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants

Time frame: Up to approximately 47 months. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab Monotherapy (Pembro Mono) n = 0	Pembrolizumab + Chemotherapy (Pembro Combo) n = 281	Cetuximab + Chemotherapy (Control) n = 278
Value	–	4.9 (4.7 to 6.1)	5.2 (4.9 to 6.1)

Pembrolizumab + Chemotherapy (Pembro Combo) vs Cetuximab + Chemotherapy (Control): Hazard Ratio (HR): 0.93 (95% CI 0.78 to 1.11), p = 0.21211, Regression, Cox

Population analysed: All participants in the ITT population randomized to either the pembro combo arm or control arm during active enrollment were analyzed. 22 participants in the control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.

Primary outcome: Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1

Time frame: Up to approximately 47 months. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab Monotherapy (Pembro Mono) n = 0	Pembrolizumab + Chemotherapy (Pembro Combo) n = 242	Cetuximab + Chemotherapy (Control) n = 235
Value	–	5.1 (4.7 to 6.2)	5.0 (4.8 to 6.0)

Pembrolizumab + Chemotherapy (Pembro Combo) vs Cetuximab + Chemotherapy (Control): Hazard Ratio (HR): 0.84 (95% CI 0.69 to 1.02), p = 0.03697, Regression, Cox

Population analysed: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥1 were analyzed. 20 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.

Primary outcome: Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

Time frame: Up to approximately 47 months. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab Monotherapy (Pembro Mono) n = 0	Pembrolizumab + Chemotherapy (Pembro Combo) n = 126	Cetuximab + Chemotherapy (Control) n = 110
Value	–	5.8 (4.7 to 7.6)	5.3 (4.9 to 6.3)

Pembrolizumab + Chemotherapy (Pembro Combo) vs Cetuximab + Chemotherapy (Control): Hazard Ratio (HR): 0.76 (95% CI 0.58 to 1.01), p = 0.02951, Regression, Cox

Population analysed: Participants in the ITT population randomized to either pembro combo arm or control arm during active enrollment with CPS ≥20 were analyzed. 12 participants in control arm enrolled during an enrollment pause of the pembro combo arm were excluded. Per protocol, pembro mono arm was compared to control arm separately and not included in this analysis.

Primary outcome: Pembro Combo vs Control: Overall Survival (OS) in All Participants

Time frame: Up to approximately 47 months. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab Monotherapy (Pembro Mono) n = 0	Pembrolizumab + Chemotherapy (Pembro Combo) n = 281	Cetuximab + Chemotherapy (Control) n = 278
Value	–	13.0 (10.9 to 14.7)	10.7 (9.3 to 11.7)

Pembrolizumab + Chemotherapy (Pembro Combo) vs Cetuximab + Chemotherapy (Control): Hazard Ratio (HR): 0.72 (95% CI 0.60 to 0.87), p = 0.00025, Regression, Cox

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 98 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pembrolizumab Monotherapy (First Course)	123 of 300 (41%)	265 of 300 (88.3%)	260 of 301
Pembrolizumab + Chemotherapy (First Course)	165 of 276 (59.8%)	266 of 276 (96.4%)	242 of 281
Cetuximab + Chemotherapy (Control)	142 of 287 (49.5%)	278 of 287 (96.9%)	282 of 300
Pembrolizumab Monotherapy (Second Course)	1 of 8 (12.5%)	6 of 8 (75%)	5 of 8
Pembrolizumab + Chemotherapy (Second Course)	2 of 6 (33.3%)	6 of 6 (100%)	5 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 40262400Tahara M, Greil R, Rischin D, Harrington KJ, Burtness B, de Castro G, Psyrri A, Brana I, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak WZW, Lin J, Gumuscu B, Lerman N, Soulieres D. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study. Eur J Cancer. 2025 May 15;221:115395. doi: 10.1016/j.ejca.2025.115395. Epub 2025 Apr 4.
Derived from this study: PubMed 39382718Oridate N, Takahashi S, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K, Yokota T, Yamazaki T, Takahashi M, Ueda T, Hanai N, Yamaguchi H, Hara H, Yoshizaki T, Yasumatsu R, Nakayama M, Shiga K, Fujii T, Mitsugi K, Takahashi K, Nohata N, Gumuscu B, Lerman N, Tahara M. First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE-048. Int J Clin Oncol. 2024 Dec;29(12):1825-1839. doi: 10.1007/s10147-024-02632-x. Epub 2024 Oct 9.
Derived from this study: PubMed 37699333Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
Derived from this study: PubMed 36264378Takahashi S, Oridate N, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K, Yokota T, Yamazaki T, Takahashi M, Ueda T, Hanai N, Yamaguchi H, Hara H, Yoshizaki T, Yasumatsu R, Nakayama M, Shiga K, Fujii T, Mitsugi K, Takahashi K, Nohata N, Gumuscu B, Swaby RF, Tahara M. First-line pembrolizumab +/- chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048. Int J Clin Oncol. 2022 Dec;27(12):1805-1817. doi: 10.1007/s10147-022-02233-6. Epub 2022 Oct 20.
Derived from this study: PubMed 36219809Harrington KJ, Burtness B, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11.
Derived from this study: PubMed 35381576Rischin D, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak WZW, Hong RL, Mendoza RG, Jia L, Chirovsky D, Norquist J, Jin F, Burtness B. Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048. Oral Oncol. 2022 May;128:105815. doi: 10.1016/j.oraloncology.2022.105815. Epub 2022 Apr 2.
Derived from this study: PubMed 35333599Burtness B, Rischin D, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Ge J, Swaby RF, Gumuscu B, Harrington K. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. J Clin Oncol. 2022 Jul 20;40(21):2321-2332. doi: 10.1200/JCO.21.02198. Epub 2022 Mar 25.
Derived from this study: PubMed 31679945Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
Merck Clinical Trials InformationLink provided by the sponsor.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Cisplatin and Carboplatin in people with Recurrent Head and Neck Cancer and Metastatic Head and Neck Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants (time frame: Up to approximately 47 months). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02358031, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.