Head and Neck Squamous Cell CancerPhase 3NCT02252042

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

A Phase 3 study testing Pembrolizumab, Methotrexate and Docetaxel in people with Head and Neck Squamous Cell 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

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Head and Neck Squamous Cell Cancer
What is being tested?: Pembrolizumab, Methotrexate and Docetaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 495 participants
Where: No sites listed yet
Study dates: 17 Nov 2014to 15 Aug 2022
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

Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
Failure of prior platinum therapy
Radiographically-measurable disease based on RECIST 1.1
Tumor tissue available for PD-L1 biomarker analysis
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ function
Female participants of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care
Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care

Who cannot join

Disease is suitable for local therapy administered with curative intent
Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization
Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
Not recovered from adverse events due to therapy more than 4 weeks earlier
Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1, or not recovered from adverse events due to agents administered more than 4 weeks earlier

Show all 17Show fewer

Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast cancers
Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active, non-infectious pneumonitis
Active infection requiring systemic therapy
Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial therapy according to local standard of care
Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial
Human immunodeficiency virus (HIV)
Hepatitis B or C
Live vaccine within 30 days of planned start of study therapy

About this study

Official title: A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer

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

Conditions: Head and Neck Squamous Cell Cancer
Being tested: Pembrolizumab, Methotrexate, Docetaxel, Cetuximab
Keywords: Squamous cell carcinoma, Head and neck carcinoma, Programmed Cell Death-1 (PD1, PD-1),, Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
Medical subject headings: Carcinoma, Squamous Cell, 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 MK-3475, KEYTRUDA®
200 mg intravenous (IV) on Day 1 of each 3-week cycle.
MethotrexateDrug
40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle
DocetaxelDrug
75 mg/m^2 IV on Day 1 of each 3- week cycle
CetuximabBiological
400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.

Study groups in NCT02252042
Study group	Role	What they receive
Pembroliziumab	Experimental	Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion. Receives: Biological: Pembrolizumab
Standard Treatment	Active comparator	Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle. Receives: Drug: Methotrexate; Drug: Docetaxel; Biological: Cetuximab

What is being measured

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

Initial Overall Survival (OS) for 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 to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
Measured: Up to approximately 2 years
Updated Final OS for 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 to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years

Secondary outcomes (15)

OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
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. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
Duration of Response (DOR) Per RECIST 1.1 in All Participants
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
Time to Progression (TTP) Per RECIST 1.1 in All Participants
TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
PFS Per Modified RECIST in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Measured: Up to approximately 2 years
Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
Measured: Up to approximately 33 months
Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.
Measured: Up to approximately 33 months
Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented.
Measured: Up to approximately 30 months
Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.
Measured: Up to approximately 30 months

Timeline

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

17 Nov 201415 Aug 2022

First posted29 Sep 2014 (estimated)
Study start17 Nov 2014
Primary completion15 May 2017
Study completion15 Aug 2022

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 (5)Papers the sponsor has linked to this study.
Other trials for Head and Neck Squamous Cell 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: 495 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02252042
Sponsor's protocol ID: 3475-040
Other IDs: MK-3475-040, 2014-001749-26, 2014
Status last verified: Jun 2023
First submitted: 25 Sep 2014
Last updated: 17 Jul 2023
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

Xin W, Ding H, Fang Q, Zheng X, Tong Y, Xu G, Yang G. Cost-effectiveness of pembrolizumab for treatment of platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma in China: an economic analysis based on a randomised, open-label, phase III trial. BMJ Open. 2020 Dec 18;10(12):e038867. doi: 10.1136/bmjopen-2020-038867.
PubMed 33371020
Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulieres D, Le Tourneau C, Licitra L, Burtness B, Swaby R. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol. 2021 Mar;34(3):532-541. doi: 10.1038/s41379-020-00710-9. Epub 2020 Nov 25.
PubMed 33239737
Pai SI, Faivre S, Licitra L, Machiels JP, Vermorken JB, Bruzzi P, Gruenwald V, Giglio RE, Leemans CR, Seiwert TY, Soulieres D. Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). J Immunother Cancer. 2019 Apr 3;7(1):96. doi: 10.1186/s40425-019-0578-0.
PubMed 30944020
Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8. Epub 2018 Nov 30.
PubMed 30509740
Guo T, Califano JA. Molecular biology and immunology of head and neck cancer. Surg Oncol Clin N Am. 2015 Jul;24(3):397-407. doi: 10.1016/j.soc.2015.03.002. Epub 2015 Apr 20.
PubMed 25979390

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung 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
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
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
Not yet recruiting
Tumoral Versus Luminal Microbiome in Head and Neck Squamous Cell Carcinoma
Squamous Cell Cancer of Head and Neck (SCCHN)

All Head and Neck Squamous Cell Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
ClinicalTrials.gov ID: NCT02252042
Acronym / sponsor ID: 3475-040
Conditions: Head and Neck Squamous Cell Cancer
Keywords: Squamous cell carcinoma, Head and neck carcinoma, Programmed Cell Death-1 (PD1, PD-1),, Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 495 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 17 Nov 2014 (actual)
Primary completion: 15 May 2017 (actual)
Study completion: 15 Aug 2022 (actual)
First posted: 29 Sep 2014 (estimated)
Results: Posted 13 Aug 2018

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Pembroliziumab	Experimental	Biological: PembrolizumabParticipants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion.
Standard Treatment	Active comparator	Drug: Methotrexate, Drug: Docetaxel, Biological: CetuximabParticipants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.

Who may qualify

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

Key inclusion criteria (8 listed)

Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
Failure of prior platinum therapy
Radiographically-measurable disease based on RECIST 1.1
Tumor tissue available for PD-L1 biomarker analysis
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key exclusion criteria (17 listed)

Disease is suitable for local therapy administered with curative intent
Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization
Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
Not recovered from adverse events due to therapy more than 4 weeks earlier

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: MK-3475, KEYTRUDA®200 mg intravenous (IV) on Day 1 of each 3-week cycle.	Biological	Pembroliziumab
Methotrexate40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle	Drug	Standard Treatment
Docetaxel75 mg/m^2 IV on Day 1 of each 3- week cycle	Drug	Standard Treatment
Cetuximab400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.	Biological	Standard Treatment

Primary outcome

Initial Overall Survival (OS) for All Participants
Time frame: Up to approximately 2 years
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
Updated Final OS for All Participants
Time frame: Up to approximately 2 years
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.

15 secondary outcomes

OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
Time frame: Up to approximately 2 years
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
Time frame: Up to approximately 2 years
PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 2 years
Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
Time frame: Up to approximately 2 years
ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 2 years
Duration of Response (DOR) Per RECIST 1.1 in All Participants
Time frame: Up to approximately 2 years
DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 2 years
Time to Progression (TTP) Per RECIST 1.1 in All Participants
Time frame: Up to approximately 2 years
TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 2 years
PFS Per Modified RECIST in All Participants
Time frame: Up to approximately 2 years
PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 2 years
Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
Time frame: Up to approximately 33 months
Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 33 months
Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
Time frame: Up to approximately 30 months
Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
Time frame: Up to approximately 30 months

Results and safety

Results posted to the registry on 13 Aug 2018, 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	247	0
Standard Treatment	248	0

Primary outcome: Initial Overall Survival (OS) for All Participants

Time frame: Up to approximately 2 years. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab n = 247	Standard Treatment n = 248
Value	8.4 (6.5 to 9.4)	7.1 (5.9 to 8.1)

Pembrolizumab vs Standard Treatment: Hazard Ratio (HR): 0.82 (95% CI 0.67 to 1.01), p = 0.03160, Log Rank

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

Primary outcome: Updated Final OS for All Participants

Time frame: Up to approximately 2 years. Median (95% Confidence Interval). Unit: Months

Measure	Pembrolizumab n = 247	Standard Treatment n = 248
Value	8.4 (6.4 to 9.4)	6.9 (5.9 to 8.0)

Pembrolizumab vs Standard Treatment: Hazard Ratio (HR): 0.80 (95% CI 0.65 to 0.98), p = 0.01605, Log Rank

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

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 92 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pembrolizumab First Course	110 of 246 (44.7%)	215 of 246 (87.4%)	228 of 247
Standard Treatment First Course	92 of 234 (39.3%)	211 of 234 (90.2%)	243 of 248
Pembrolizumab Second Course	0 of 2 (0%)	0 of 2 (0%)	2 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33371020Xin W, Ding H, Fang Q, Zheng X, Tong Y, Xu G, Yang G. Cost-effectiveness of pembrolizumab for treatment of platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma in China: an economic analysis based on a randomised, open-label, phase III trial. BMJ Open. 2020 Dec 18;10(12):e038867. doi: 10.1136/bmjopen-2020-038867.
Derived from this study: PubMed 33239737Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulieres D, Le Tourneau C, Licitra L, Burtness B, Swaby R. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol. 2021 Mar;34(3):532-541. doi: 10.1038/s41379-020-00710-9. Epub 2020 Nov 25.
Derived from this study: PubMed 30944020Pai SI, Faivre S, Licitra L, Machiels JP, Vermorken JB, Bruzzi P, Gruenwald V, Giglio RE, Leemans CR, Seiwert TY, Soulieres D. Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). J Immunother Cancer. 2019 Apr 3;7(1):96. doi: 10.1186/s40425-019-0578-0.
Derived from this study: PubMed 30509740Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8. Epub 2018 Nov 30.
Derived from this study: PubMed 25979390Guo T, Califano JA. Molecular biology and immunology of head and neck cancer. Surg Oncol Clin N Am. 2015 Jul;24(3):397-407. doi: 10.1016/j.soc.2015.03.002. Epub 2015 Apr 20.
Merck Clinical Trials InformationLink provided by the sponsor.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Head and Neck Squamous Cell Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung 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
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
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
Not yet recruiting
Tumoral Versus Luminal Microbiome in Head and Neck Squamous Cell Carcinoma
Squamous Cell Cancer of Head and Neck (SCCHN)

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, Methotrexate and Docetaxel in people with Head and Neck Squamous Cell 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 8 inclusion and 17 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 17 Jul 2023. 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 13 Aug 2018). 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?

Initial Overall Survival (OS) for All Participants (time frame: Up to approximately 2 years). The study lists 2 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 NCT02252042, which also lists 5 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 17 Jul 2023.