Description:
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).
Title
- Brief Title: Pembrolizumab (MK-3475) Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)
- Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants With High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)
Clinical Trial IDs
- ORG STUDY ID:
3475-630
- SECONDARY ID:
2018-001974-76
- SECONDARY ID:
MK-3475-630
- SECONDARY ID:
KEYNOTE-630
- NCT ID:
NCT03833167
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab 400 mg | KEYTRUDA®, MK-3475 | Pembrolizumab |
Placebo | | Placebo |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Pembrolizumab | Experimental | 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. | |
Placebo | Placebo Comparator | 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. | |
Eligibility Criteria
Inclusion Criteria:
- Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary
site of malignancy (metastatic skin involvement from another primary cancer or from an
unknown primary cancer is not permitted)
- Has histologically confirmed 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 woman of childbearing potential (WOCBP)
- 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
Exclusion Criteria:
- Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease
before randomization
- Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell
carcinoma) that has not been definitively treated with surgery or radiation; Bowen's
disease; Merkel cell carcinoma; or melanoma
- Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-
PD-L1, or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent
directed to another co-stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic
T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
- Has received prior systemic anticancer therapy including investigational agents for
cSCC ≤4 weeks prior to randomization
- Has not recovered from all radiation-related toxicities and has not had radiation
pneumonitis
- Has received a live vaccine ≤30 days prior to the first dose of study intervention
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device ≤4 weeks prior to the first dose of study
intervention
- Has an active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is
detected) 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 intervention
- Has had an allogeneic tissue/solid organ transplant
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy |
Time Frame: | Up to approximately 60 months |
Safety Issue: | |
Description: | RFS 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. |
Secondary Outcome Measures
Measure: | Overall Survival (OS) |
Time Frame: | Up to approximately 60 months |
Safety Issue: | |
Description: | OS is the time from randomization to death due to any cause. |
Measure: | Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score |
Time Frame: | Baseline and up to approximately 60 months |
Safety Issue: | |
Description: | Change from baseline in the score of EORTC QLQ-C30 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, which contains 30 items and measures 5 functioning dimensions (physical, role, emotional, cognitive, and social), 3 symptom items (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Scores ranged from 0 -100. For functional and global quality of life (QoL) scales, higher scores meant a better level of function. For symptom-oriented scales, a higher score meant more severe symptoms and a decrease in QoL. |
Measure: | 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 |
Time Frame: | Baseline and up to approximately 60 months |
Safety Issue: | |
Description: | 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. |
Measure: | Percentage of Participants Who Experience an Adverse Event (AE) |
Time Frame: | Up to approximately 63 months |
Safety Issue: | |
Description: | 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 will be presented. |
Measure: | Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) |
Time Frame: | Up to approximately 38 months |
Safety Issue: | |
Description: | 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 will be presented. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial 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
Last Updated
August 30, 2021