Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
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 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.
Interventions
BIOLOGICALpembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 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. |
| 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 | 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. |
| Number of Participants Experiencing an Adverse Event (AE) | 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. |
| Number of Participants Discontinuing Study Drug Due to an AE | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 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. |
| 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 | 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. |
| 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 | 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. |
| Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 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. |
| 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 | 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. |
| 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 | 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. |
| Overall Survival (OS) in All Participants | 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. |
| Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants | 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. |
| Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants | 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. |
| 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 | 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. |
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors | 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. |
| Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 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. |
| 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 | 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. |
Participant flow
Recruitment details
Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. Per protocol, response or progression during the second course of pembrolizumab was not counted towards efficacy outcome measures and adverse events during the second course of pembrolizumab were not counted towards safety outcome measures.
Pre-assignment details
Final analyses for all primary outcome measures were done at the protocol-specified primary outcome measure met date. The analyses for all secondary outcome measures and the collection of adverse events were updated at the end of study date. One participant allocated to receive pembrolizumab did not receive treatment. This participant was not eligible for safety or efficacy analysis.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 3-week cycle for up to 24 months. Participants who stopped pembrolizumab as a result of obtaining a CR or those who stopped after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, were eligible for up to an additional 1 year of treatment after progressive disease if they met the criteria for re-treatment. | 172 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Allocated but not treated | 1 |
| Overall Study | Death | 151 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Participation in Study Discontinued by Sponsor | 8 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Pembrolizumab |
|---|---|
| Age, Continuous | 61.1 Years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status <1% | 46 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status ≥1 - <50% | 77 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status ≥50% | 44 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status Unknown | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 153 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 138 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 153 / 172 | 2 / 3 |
| other Total, other adverse events | 158 / 171 | 3 / 3 |
| serious Total, serious adverse events | 87 / 171 | 1 / 3 |
Outcome results
Primary
Number of Participants Discontinuing Study Drug Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with 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.
Time frame: Up to 24 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Number of Participants Discontinuing Study Drug Due to an AE | 24 Participants |
Primary
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with 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.
Time frame: Up to 27 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Number of Participants Experiencing an Adverse Event (AE) | 166 Participants |
Primary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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.
Time frame: Up to 36 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 16.4 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Primary
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
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.
Time frame: Up to 36 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥50%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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 | 27.3 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Secondary
Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 16.4 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥1%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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 | 18.2 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥50%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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 | 27.3 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Secondary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a HPV-positive tumor
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors | 14.1 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: 0.0027exact binomial distribution
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥1%
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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 | 18.2 Percentage of participants |
Comparison: Analysis comparing the ORR for pembrolizumab to a fixed efficacy target of 5% using an exact test of binomial distributionp-value: <0.001exact binomial distribution
Secondary
Overall Survival (OS) in All Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in All Participants | 8.5 Months |
Secondary
Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a combined positive score ≥1%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants | 9.0 Months |
Secondary
Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥50%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants | 6.9 Months |
Secondary
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 2.1 Months |
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a combined positive score ≥1%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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 | 2.1 Months |
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥50%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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 | 2.1 Months |
Secondary
Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a best overall response as confirmed complete response or partial response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 15.7 Months |
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a combined positive score ≥1% and a best overall response as confirmed complete response or partial response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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 | 15.7 Months |
Secondary
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
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.
Time frame: Up to 76.9 months
Population: All participants who received at least one dose of study treatment with a tumor proportion score ≥50% and a best overall response as confirmed complete response or partial response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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 | 22.8 Months |