Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02252042 |
Recruitment Status :
Completed
First Posted : September 29, 2014
Results First Posted : August 13, 2018
Last Update Posted : July 17, 2023
|
Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Study Type | Interventional |
---|---|
Study Design | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Head and Neck Squamous Cell Cancer |
Interventions |
Biological: Pembrolizumab Drug: Methotrexate Drug: Docetaxel Biological: Cetuximab |
Enrollment | 495 |
Participant Flow
Recruitment Details | |
Pre-assignment Details | 495 participants were randomized 1:1 to receive either pembrolizumab or standard treatment. Per protocol, response/progression or adverse events (AEs) that occurred during the second course of pembrolizumab were not counted towards efficacy outcome measures or safety outcome measures, respectively. |
Arm/Group Title | Pembrolizumab | Standard Treatment |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could 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. |
Period Title: Overall Study | ||
Started | 247 | 248 |
Received First Course of Pembrolizumab | 246 [1] | 234 [2] |
Received Second Course of Pembrolizumab | 2 | 0 |
Completed | 0 | 0 |
Not Completed | 247 | 248 |
Reason Not Completed | ||
Adverse Event | 9 | 6 |
Death | 209 | 217 |
Physician Decision | 0 | 2 |
Transferred to Extension Study | 7 | 1 |
Did Not Continue on Extension Study | 7 | 2 |
Withdrawal by Subject | 15 | 20 |
[1]
1 participant was randomized but did not receive study treatment.
[2]
14 participants were randomized but did not receive study treatment.
|
Baseline Characteristics
Arm/Group Title | Pembrolizumab | Standard Treatment | Total | |
---|---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | Participants received standard treatment of either methotrexate 40 mg/m^2 IV (could 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. | Total of all reporting groups | |
Overall Number of Baseline Participants | 247 | 248 | 495 | |
Baseline Analysis Population Description |
[Not Specified]
|
|||
Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
60.3 (9.8) | 60.2 (8.6) | 60.2 (9.2) | ||
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
Female |
40 16.2%
|
43 17.3%
|
83 16.8%
|
|
Male |
207 83.8%
|
205 82.7%
|
412 83.2%
|
|
Ethnicity (NIH/OMB)
Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
Hispanic or Latino |
21 8.5%
|
12 4.8%
|
33 6.7%
|
|
Not Hispanic or Latino |
182 73.7%
|
195 78.6%
|
377 76.2%
|
|
Unknown or Not Reported |
44 17.8%
|
41 16.5%
|
85 17.2%
|
|
Race (NIH/OMB)
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
American Indian or Alaska Native |
2 0.8%
|
0 0.0%
|
2 0.4%
|
|
Asian |
15 6.1%
|
16 6.5%
|
31 6.3%
|
|
Native Hawaiian or Other Pacific Islander |
0 0.0%
|
0 0.0%
|
0 0.0%
|
|
Black or African American |
3 1.2%
|
7 2.8%
|
10 2.0%
|
|
White |
206 83.4%
|
207 83.5%
|
413 83.4%
|
|
More than one race |
4 1.6%
|
3 1.2%
|
7 1.4%
|
|
Unknown or Not Reported |
17 6.9%
|
15 6.0%
|
32 6.5%
|
|
[1]
Measure Description: The race of participants is presented.
|
||||
Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS)
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
TPS = 0% |
103 41.7%
|
93 37.5%
|
196 39.6%
|
|
1% ≤ TPS <50% |
79 32.0%
|
87 35.1%
|
166 33.5%
|
|
TPS ≥ 50% |
64 25.9%
|
65 26.2%
|
129 26.1%
|
|
Missing |
1 0.4%
|
3 1.2%
|
4 0.8%
|
|
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a TPS ≥50% were classified as PD-L1 strongly positive and participants with a TPS <50% were classified as not strongly positive.
|
||||
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
EGOG PS=0 |
71 28.7%
|
68 27.4%
|
139 28.1%
|
|
ECOG PS=1 |
176 71.3%
|
179 72.2%
|
355 71.7%
|
|
ECOG PS=2 |
0 0.0%
|
1 0.4%
|
1 0.2%
|
|
[1]
Measure Description: Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature; Grade 2: Ambulatory & capable of all selfcare but unable to carry out any work activities, up & about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.
|
||||
Human Papillomavirus (HPV) Tumor Status
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
Positive HPV Status |
61 24.7%
|
57 23.0%
|
118 23.8%
|
|
Negative HPV Status |
186 75.3%
|
191 77.0%
|
377 76.2%
|
|
[1]
Measure Description: Participants were assessed for the presence or absence of HPV in their tumors.
|
||||
PD-L1 Combined Positive Score (CPS) Status
[1] Measure Type: Count of Participants Unit of measure: Participants |
||||
Number Analyzed | 247 participants | 248 participants | 495 participants | |
PD-L1 CPS <1 |
50 20.2%
|
54 21.8%
|
104 21.0%
|
|
PD-L1 CPS ≥1 |
196 79.4%
|
191 77.0%
|
387 78.2%
|
|
Missing |
1 0.4%
|
3 1.2%
|
4 0.8%
|
|
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a CPS ≥1 were classified as PD-L1 positive and participants with a CPS <1 were classified as PD-L1 negative.
|
Outcome Measures
Adverse Events
Limitations and Caveats
[Not Specified]
More Information
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Name/Title: | Senior Vice President, Global Clinical Development |
Organization: | Merck Sharp & Dohme LLC |
Phone: | 1-800-672-6372 |
EMail: | ClinicalTrialsDisclosure@merck.com |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Merck Sharp & Dohme LLC |
ClinicalTrials.gov Identifier: | NCT02252042 |
Other Study ID Numbers: |
3475-040 MK-3475-040 ( Other Identifier: Merck Protocol Number ) 2014-001749-26 ( EudraCT Number ) |
First Submitted: | September 25, 2014 |
First Posted: | September 29, 2014 |
Results First Submitted: | May 4, 2018 |
Results First Posted: | August 13, 2018 |
Last Update Posted: | July 17, 2023 |