Carcinoma, Squamous Cell
Conditions
Keywords
Programmed Cell Death-1 (PD-1), Programmed Cell Death 1, PD1, Programmed Cell Death Ligand 1 (PD-L1), Programmed Cell Death Ligand 2 (PD-L2), PDL1, PDL2
Brief summary
This is a randomized, double-blind, study that compares pembrolizumab (MK-3475) with placebo given as adjuvant therapy in participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) that have undergone surgery with curative intent in combination with radiotherapy. The primary hypothesis is that pembrolizumab is superior to placebo in increasing recurrence free survival (RFS).
Interventions
BIOLOGICALPembrolizumab
400 mg IV infusion
DRUGPlacebo
Placebo-matched IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria include, but are not limited to: * Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted) * Has histologically confirmed locally advanced cutaneous squamous cell carcinoma (LA cSCC) with ≥1 high-risk feature(s) as the primary site of malignancy * Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided * Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization * Has received an adequate post-op dose of RT (either hypofractionated or conventional) * Is disease free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization * Is not pregnant or breastfeeding * Is not a person of childbearing potential (POCBP) * Has a negative pregnancy test ≤72 hours before the first dose of study intervention. * Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing * Has a life expectancy of \>3 months * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ≤10 days prior to the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy | Up to approximately 62 months | RFS as assessed by investigator was defined as the time between the date of randomization to the date of first local or regional recurrence of the index lesion, distant metastasis, or death due to any cause; whichever occurred first. Participants were analyzed in the treatment group to which they were randomized. RFS as assessed by investigator is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 62 months | OS is the time from randomization to death due to any cause. Participants were analyzed in the treatment group to which they were randomized. OS is presented. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | Baseline and up to approximately 60 months | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score is presented. |
| Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score | Baseline and up to approximately 60 months | Change from baseline in the score of EORTC QLQ-C30 Items 1-5 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function. Participants were analyzed in the treatment group to which they were randomized. Change from baseline in EORTC QLQ-C30 physical functioning is presented. |
| Percentage of Participants Who Experience an Adverse Event (AE) | Up to approximately 62 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who experience at least one AE is presented. |
| Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | Up to approximately 19 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE is presented. |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Mexico, New Zealand, Norway, Poland, Portugal, Romania, Russia, Spain, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Of the 450 participants randomized, 448 received study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants receive 400 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants that complete 9 cycles of pembrolizumab and experience biopsy-proven-disease recurrence may be eligible to receive up to 18 additional cycles of pembrolizumab in an open-label design. | 225 |
| Placebo Participants receive placebo by IV infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants treated with placebo who experience biopsy-proven-disease recurrence may be eligible to receive up to 18 cycles of pembrolizumab in an open-label design. | 225 |
| Total | 450 |
Baseline characteristics
| Characteristic | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 70.3 Years STANDARD_DEVIATION 10.8 | 69.2 Years STANDARD_DEVIATION 10.7 | 69.7 Years STANDARD_DEVIATION 10.7 |
| Cortical Bone Invasion Missing | 1 Participants | 0 Participants | 1 Participants |
| Cortical Bone Invasion No | 203 Participants | 206 Participants | 409 Participants |
| Cortical Bone Invasion Yes | 21 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 47 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 140 Participants | 148 Participants | 288 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 39 Participants | 30 Participants | 69 Participants |
| Extracapsular Extension Missing Data | 1 Participants | 0 Participants | 1 Participants |
| Extracapsular Extension No | 135 Participants | 127 Participants | 262 Participants |
| Extracapsular Extension Yes | 89 Participants | 98 Participants | 187 Participants |
| Prior Systemic Therapy No | 209 Participants | 208 Participants | 417 Participants |
| Prior Systemic Therapy Yes | 16 Participants | 17 Participants | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 14 Participants | 11 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 35 Participants | 28 Participants | 63 Participants |
| Race (NIH/OMB) White | 174 Participants | 181 Participants | 355 Participants |
| Sex: Female, Male Female | 41 Participants | 41 Participants | 82 Participants |
| Sex: Female, Male Male | 184 Participants | 184 Participants | 368 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 34 / 225 | 14 / 225 | 1 / 2 | 10 / 30 |
| other Total, other adverse events | 175 / 224 | 143 / 224 | 2 / 2 | 23 / 30 |
| serious Total, serious adverse events | 55 / 224 | 43 / 224 | 0 / 2 | 15 / 30 |
Outcome results
Primary
Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy
RFS as assessed by investigator was defined as the time between the date of randomization to the date of first local or regional recurrence of the index lesion, distant metastasis, or death due to any cause; whichever occurred first. Participants were analyzed in the treatment group to which they were randomized. RFS as assessed by investigator is presented.
Time frame: Up to approximately 62 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy | 53.3 Months |
| Placebo | Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy | 53.7 Months |
p-value: 0.0724395% CI: [0.53, 1.1]Log Rank
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? and How would you rate your overall quality of life during the past week? are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score is presented.
Time frame: Baseline and up to approximately 60 months
Population: All participants who had at least one dose of study intervention and one EORTC QLQ-C30 score available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | -7.05 Score on scale |
| Placebo | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | -3.64 Score on scale |
p-value: 0.222795% CI: [-8.91, 2.09]Log Rank
Secondary
Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score
Change from baseline in the score of EORTC QLQ-C30 Items 1-5 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function. Participants were analyzed in the treatment group to which they were randomized. Change from baseline in EORTC QLQ-C30 physical functioning is presented.
Time frame: Baseline and up to approximately 60 months
Population: All participants who had at least one dose of study intervention and one EORTC QLQ-C30 score available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab | Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score | -7.60 Scores on a scale |
| Placebo | Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score | -4.71 Scores on a scale |
p-value: 0.187495% CI: [-7.19, 1.42]Log Rank
Secondary
Overall Survival (OS)
OS is the time from randomization to death due to any cause. Participants were analyzed in the treatment group to which they were randomized. OS is presented.
Time frame: Up to approximately 62 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) | NA Months |
| Placebo | Overall Survival (OS) | NA Months |
95% CI: [0.87, 2.48]
Secondary
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE is presented.
Time frame: Up to approximately 19 months
Population: All randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | 10.3 Percentage of participants |
| Placebo | Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | 4.0 Percentage of participants |
Secondary
Percentage of Participants Who Experience an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who experience at least one AE is presented.
Time frame: Up to approximately 62 months
Population: All randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of Participants Who Experience an Adverse Event (AE) | 94.2 Percentage of participants |
| Placebo | Percentage of Participants Who Experience an Adverse Event (AE) | 88.8 Percentage of participants |