- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02255097
Study of MK-3475 (Pembrolizumab) in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma After Treatment With Platinum-based and Cetuximab Therapy (MK-3475-055/KEYNOTE-055)
A Phase II Clinical Trial of Single Agent Pembrolizumab (MK-3475) in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Who Have Failed Platinum and Cetuximab
This is a study of single-agent pembrolizumab (MK-3475) in participants with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on platinum-based and cetuximab therapy. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful objective response rate (ORR).
With protocol amendment 05 (02-Jan-2018), once study participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Histologically- or cytologically-confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
- Tumor progression or recurrence within 6 months of the last dose of any number of platinum-based and cetuximab therapy lines in the adjuvant, primary, recurrent, or metastatic setting; must be resistant (not responding) to both platinum and cetuximab
- Available tissue for biomarker analysis
- Measurable disease based on RECIST 1.1 as determined by central review
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
- Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use 2 adequate methods of contraception starting with the screening visit through 120 days after the last dose of pembrolizumab
- Male participants with a female partner(s) of childbearing potential must be willing to use 2 adequate methods of contraception from screening through 120 days after the last dose of pembrolizumab
Exclusion criteria:
- Disease that is suitable for local therapy administered with curative intent
- Currently receiving treatment in a study of an investigational agent or using an investigational device <= 4 weeks prior to the first dose of trial medication
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial medication
- Not recovered from AEs due to a previously administered therapy
- Known additional malignancy that is progressing or requires active treatment excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cancer
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- 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 medication
- Human immunodeficiency virus (HIV)
- Hepatitis B or C
- Received live vaccine within 30 days of planned start of study therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Time Frame: Up to 36 months
|
ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
Participants with missing data were considered non-responders.
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Up to 36 months
|
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 36 months
|
Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1.
The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%.
ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
Participants with missing data were considered non-responders.
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Up to 36 months
|
Number of Participants Experiencing an Adverse Event (AE)
Time Frame: Up to 27 months
|
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 treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product.
Worsening of a preexisting condition temporally associated with the use of the product was also an AE.
A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event.
Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
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Up to 27 months
|
Number of Participants Discontinuing Study Drug Due to an AE
Time Frame: Up to 24 months
|
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 treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product.
Worsening of a preexisting condition temporally associated with the use of the product was also an AE.
A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event.
Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
|
Up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1.
PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%.
ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
Participants with missing data were considered non-responders.
|
Up to 76.9 months
|
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors
Time Frame: Up to 76.9 months
|
Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1.
ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
Participants with missing data were considered non-responders.
|
Up to 76.9 months
|
Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Time Frame: Up to 76.9 months
|
ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression.
PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started.
Participants with missing data were considered non-responders.
|
Up to 76.9 months
|
Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1.
PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%.
ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression.
PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started.
Participants with missing data were considered non-responders.
|
Up to 76.9 months
|
Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1.
PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%.
ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference.
If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression.
PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started.
Participants with missing data were considered non-responders.
|
Up to 76.9 months
|
Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Time Frame: Up to 76.9 months
|
DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study).
DOR was censored at the last tumor assessment date if a responder did not have PD or death.
Non-responders were not included in the analysis.
The lower and upper limits were estimated at the time of data cutoff.
DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
|
Up to 76.9 months
|
Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1.
PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%.
DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study).
DOR was censored at the last tumor assessment date if a responder did not have PD or death.
Non-responders were not included in the analysis.
The lower and upper limits were estimated at the time of data cutoff.
DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
|
Up to 76.9 months
|
Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1.
PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%.
DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study).
DOR was censored at the last tumor assessment date if a responder did not have PD or death.
Non-responders were not included in the analysis.
The lower and upper limits were estimated at the time of data cutoff.
DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
|
Up to 76.9 months
|
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Time Frame: Up to 76.9 months
|
PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first.
Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions.
PFS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
|
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a positive PD-L1 expression status were evaluated for PFS.
PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%.
PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first.
Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions.
PFS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
|
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1.
PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%.
PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first.
Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions.
PFS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
|
Overall Survival (OS) in All Participants
Time Frame: Up to 76.9 months
|
OS was defined as the time from the first day of study treatment to death due to any cause.
OS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
|
Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a positive PD-L1 expression status were evaluated for OS.
PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%.
OS was defined as the time from the first day of study treatment to death due to any cause.
OS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
|
Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
Time Frame: Up to 76.9 months
|
Participants with a strong PD-L1 expression status were evaluated for OS.
PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%.
OS was defined as the time from the first day of study treatment to death due to any cause.
OS was analyzed by the Kaplan-Meier method for censored data and reported in months.
Participant data were censored at last assessment.
|
Up to 76.9 months
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
- Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
- Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Shu X, Cheng JD, Haddad R. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol. 2017 May 10;35(14):1542-1549. doi: 10.1200/JCO.2016.70.1524. Epub 2017 Mar 22.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3475-055
- 2014-002447-18 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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