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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)

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ClinicalTrials.gov Identifier: NCT02255097
Recruitment Status : Active, not recruiting
First Posted : October 2, 2014
Results First Posted : July 6, 2017
Last Update Posted : April 2, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

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 04 (30-Nov-2017), 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.


Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Biological: pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 24, 2014
Actual Primary Completion Date : April 22, 2016
Estimated Study Completion Date : January 17, 2019

Resource links provided by the National Library of Medicine


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
Biological: pembrolizumab
Other Names:
  • MK-3475
  • KEYTRUDA®




Primary Outcome Measures :
  1. Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Up to 3 years ]
    ORR was assessed by RECIST 1.1 by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  2. ORR by RECIST Version 1.1 in Strong Programmed Cell Death Ligand 1 (PD-L1)-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a strong PD L-1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD L-1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50% by IHC. ORR was assessed by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  3. Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: From first dose to last dose of treatment plus 2 months of follow-up, 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 this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any 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, was another important medical event.

  4. Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: From first dose to last dose of treatment; up to 25 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 this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any 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, was another important medical event.


Secondary Outcome Measures :
  1. ORR by RECIST 1.1 in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a positive PD L-1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD L-1 was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1% by IHC. ORR was assessed by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  2. ORR by RECIST Version 1.1 in Human Papilloma Virus (HPV)-Positive Tumors [ Time Frame: Up to 3 years ]
    Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  3. ORR by Modified RECIST Version 1.1 in All Participants [ Time Frame: Up to 3 years ]
    ORR was assessed by modified RECIST 1.1 by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  4. ORR by Modified RECIST Version 1.1 in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a positive PD L-1 expression status were evaluated for ORR by modified RECIST 1.1. The expression of PD L-1 was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1% by IHC. ORR was assessed by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  5. ORR by Modified RECIST Version 1.1 in Strong PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a strong PD L-1 expression status were evaluated for ORR by modified RECIST 1.1. The expression of PD L-1 was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50% by IHC. ORR was assessed by performing study imaging every 6-9 weeks after the first dose of study treatment. ORR was defined as the proportion 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.

  6. Response Duration (DOR) in All Participants [ Time Frame: Up to 3 years ]
    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.

  7. DOR in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a positive PD L-1 expression status were evaluated for DOR based on RECIST 1.1. The expression of PD L-1 was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1% by IHC. 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.

  8. DOR in Strong PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a strong PD L-1 expression status were evaluated for DOR based n RECIST 1.1. The expression of PD L-1 was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50% by IHC. 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.

  9. Progression-free Survival (PFS) in All Participants [ Time Frame: Up to 3 years ]
    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.

  10. PFS in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a positive PD L-1 expression status were evaluated for PFS. The expression of PD L-1 was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1% by IHC. 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.

  11. PFS in Strong PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a strong PD L-1 expression status were evaluated for PFS by modified RECIST 1.1. The expression of PD L-1 was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50% by IHC. 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.

  12. Overall Survival (OS) in All Participants [ Time Frame: Up to 3 years ]
    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.

  13. OS in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a positive PD L-1 expression status were evaluated for OS. The expression of PD L-1 was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1% by IHC. 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.

  14. OS in Strong PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
    Participants with a strong PD L-1 expression status were evaluated for OS. The expression of PD L-1 was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50% by IHC. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255097


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02255097     History of Changes
Other Study ID Numbers: 3475-055
2014-002447-18 ( EudraCT Number )
First Posted: October 2, 2014    Key Record Dates
Results First Posted: July 6, 2017
Last Update Posted: April 2, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD-1
PD1
PD-L1
PDL1

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Pembrolizumab
Cetuximab
Antineoplastic Agents