Squamous Cell Carcinoma
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in adult participants with recurrent or metastatic(R/M) cutaneous Squamous Cell Carcinoma (cSCC) or locally advanced (LA) unresectable cSCC that is not amenable to surgery and/or radiation and/or systemic therapies.
Interventions
BIOLOGICALPembrolizumab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* R/M cSCC cohort only: * Has cSCC that is either metastatic defined as disseminated disease, and/or unresectable disease that is not curable by surgery or radiation. * Has histologically-confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted). * LA cSCC cohort only: * Must be ineligible for surgical resection. * Participants who received prior radiation therapy (RT) to index site or must be deemed to be not eligible for RT. * Participants who received prior systemic therapy for curative intent are eligible regardless of regimen. * R/M cSCC cohort only: * Has metastatic disease defined as disseminated disease distant to the initial/primary site of diagnosis, and/or must have locally recurrent disease that has been previously treated (with either surgery or radiotherapy), and is not amenable to either curative surgery or radiotherapy. * Has measurable disease based on RECIST 1.1 as assessed by the central imaging vendor. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to the start of study treatment. * Has adequate organ function. * Has a tissue sample adequate for programmed death-ligand 1 (PD-L1) testing as determined by central laboratory testing prior to study allocation. * Has a life expectancy \>3 months. * Female participants of childbearing potential must agree to use an adequate method of contraception during the study treatment period and for at least 120 days after the last dose of study treatment.
Exclusion criteria
* Has cSCC that can be cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy. * Has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study, e.g. basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), melanoma. * Has had any prior allogeneic solid organ or bone marrow transplantation. * Has received prior therapy with an anti-programmed death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g. cytotoxic T-lymphocyte associated protein 4 \[CTLA-4\], Tumor necrosis factor receptor superfamily, member 4 \[OX-40\], tumor necrosis factor receptor superfamily member 9 \[CD137\]). * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study allocation. (Notes: Participants must have recovered from all AEs due to previously administered therapies to ≤ Grade 1 or baseline. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.) * Has received prior radiotherapy within 2 weeks of start of study treatment. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g. with use of disease-modifying agents, anticoagulants, corticosteroids or immunosuppressive drugs). * Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known history of Hepatitis B or known active Hepatitis C virus infection. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 32 months | ORR was defined as the percentage of participants who have best response of Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to approximately 56 months | DCR is defined as the percentage of participants who have a CR or PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease). The DCR per RECIST 1.1 as assessed by BICR is presented. |
| Progression-free Survival (PFS) | Up to approximately 56 months | PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause, whichever occurred first. PFS per RECIST 1.1 as assessed by BICR is presented. |
| Duration of Response (DOR) | Up to approximately 56 months | For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR per RECIST 1.1 as assessed by BICR is presented for all participants who experienced a confirmed CR or PR. |
| Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to approximately 56 months | An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who experienced an AE is presented. |
| Number of Participants Who Discontinued Study Treatment Due to AE | Up to approximately 56 months | An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who discontinued study treatment due to an AE is presented. |
| Overall Survival (OS) | Up to approximately 56 months | OS was defined as the time from first dose of study treatment to death due to any cause. The OS for all participants is presented. |
Countries
Australia, Canada, France, Germany, Israel, Mexico, Norway, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
There were 2 cohorts in this study and each cohort received the same dose/treatment regimen. Participant flow, baseline characteristics, and outcome measures are presented by cohort. Adverse events were pre-specified to be reported as a single group by intervention for first and second course pembrolizumab.
Participants by arm
| Arm | Count |
|---|---|
| Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) Cohort Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 doses (approximately 24 months). Eligible participants who stopped the initial course of pembrolizumab but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 105 |
| Locally Advanced Unresectable cSCC Cohort Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 doses (approximately 24 months). Eligible participants who stopped the initial course of pembrolizumab but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 54 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 70 | 24 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Sponsor's decision | 27 | 22 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Locally Advanced Unresectable cSCC Cohort | Total | Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) Cohort |
|---|---|---|---|
| Age, Continuous | 73.7 Years STANDARD_DEVIATION 12.4 | 71.3 Years STANDARD_DEVIATION 13.8 | 70.0 Years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 15 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 97 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 47 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 44 Participants | 32 Participants |
| Race (NIH/OMB) White | 40 Participants | 108 Participants | 68 Participants |
| Sex: Female, Male Female | 15 Participants | 40 Participants | 25 Participants |
| Sex: Female, Male Male | 39 Participants | 119 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 97 / 159 | 1 / 3 |
| other Total, other adverse events | 139 / 159 | 2 / 3 |
| serious Total, serious adverse events | 87 / 159 | 2 / 3 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants who have best response of Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) is presented.
Time frame: Up to approximately 32 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Objective Response Rate (ORR) | 35.2 Percentage of participants |
| Locally Advanced Unresectable cSCC Cohort | Objective Response Rate (ORR) | 51.9 Percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who have a CR or PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease). The DCR per RECIST 1.1 as assessed by BICR is presented.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Disease Control Rate (DCR) | 52.4 Percentage of participants |
| Locally Advanced Unresectable cSCC Cohort | Disease Control Rate (DCR) | 64.8 Percentage of participants |
Secondary
Duration of Response (DOR)
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR per RECIST 1.1 as assessed by BICR is presented for all participants who experienced a confirmed CR or PR.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment and had confirmed complete response or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Duration of Response (DOR) | 1.6 Months |
| Locally Advanced Unresectable cSCC Cohort | Duration of Response (DOR) | 2.7 Months |
Secondary
Number of Participants Who Discontinued Study Treatment Due to AE
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Number of Participants Who Discontinued Study Treatment Due to AE | 20 Participants |
| Locally Advanced Unresectable cSCC Cohort | Number of Participants Who Discontinued Study Treatment Due to AE | 11 Participants |
Secondary
Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Number of Participants Who Experienced One or More Adverse Events (AEs) | 102 Participants |
| Locally Advanced Unresectable cSCC Cohort | Number of Participants Who Experienced One or More Adverse Events (AEs) | 51 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from first dose of study treatment to death due to any cause. The OS for all participants is presented.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Overall Survival (OS) | 23.8 Months |
| Locally Advanced Unresectable cSCC Cohort | Overall Survival (OS) | NA Months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause, whichever occurred first. PFS per RECIST 1.1 as assessed by BICR is presented.
Time frame: Up to approximately 56 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recurrent or Metastatic Cutaneous cSCC Cohort | Progression-free Survival (PFS) | 5.7 Months |
| Locally Advanced Unresectable cSCC Cohort | Progression-free Survival (PFS) | 14.4 Months |