Resectable high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) MedDRA version: 20.0 Level: PT Classification code 10041823 Term: Squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must have 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) 2. Participant must have undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. Surgery may consist of 1 or a combination of the following: a. Resection of the primary lesion b. Any type of neck dissection(s) c. Any type of parotidectomy (superficial, total, partial) 3. Participant must have histologically confirmed LA cSCC with a high-risk feature(s) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted). High-risk features include at least 1 of the following: a) Histologically involved nodal disease that has at least 1 of the following features: • Any extracapsular extension • =3 regional lymph nodes per primary site (affected regional sites and associated draining lymph nodes) • 1-2 involved lymph nodes with any node =3 cm in greatest diameter, independent of extracapsular extension b) Any index tumor with =2 of the following high risk features: • Tumor =4 cm with a depth >6 mm • Multi-focal perineural invasion for nerves of <0.1 mm diameter or any involved nerve =0.1 mm diameter • Invasion beyond subcutaneous fat • Poor differentiation and/or sarcomatoid and/or spindle cell histology • Recurrent disease (any cSCC that recurs within 3 years in the previously surgically or topically treated area) c) Any gross cortical bone invasion or skull base invasion and/or skull base foramen invasion d) Any index tumor that is resected with microscopic residual positive surgical margins 4. Participant must have completed adjuvant RT for LA cSCC with last dose of RT =4 weeks and =16 weeks from randomization 5. Participant must have completed at least 50 Gy 25 fractions of adjuvant RT for LA cSCC prior to study entry 6. Participant is disease-free as assessed by the investigator with complete radiographic staging assessment =28 days from randomization 7. Participant is male or female and at least 18 years of age at the time of signing the informed consent 8. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis),during the intervention period and for at least 120 days after the last dose of study intervention The investigator should evaluate the potential for contraceptive method failure (ie, noncomplia
Exclusion criteria
Exclusion criteria: 1. Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization 2. 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, MCC, melanoma 3. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive 4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another costimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 5. Has received prior systemic anticancer therapy including investigational agents for cSCC within 4 weeks prior to randomization 6. Participant must have recovered from all radiation-related toxicities, not have required corticosteroids, and not have had radiation pneumonitis 7. Has received a live vaccine within 30 days prior to the first dose of study treatment.Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed 8. 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 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug 10. Has a diagnosed and/or treated additional malignancy within the past 5 years prior to randomization 11. Has known active central nervous system metastases and/or carcinomatous meningitis 12. Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients 13. 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). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 14. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis 15. Has an active infection requiring systemic therapy 16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority 17. 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 18. Has a history or cu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Recurrence-free survival (RFS) as assessed by the investigator and confirmed by biopsy;Timepoint(s) of evaluation of this end point: Up to approximately 60 months for the evaluation of recurrence-free survival;Main Objective: To compare the recurrence-free survival (RFS), as assessed by the investigator and confirmed by biopsy, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy; Secondary Objective: 1. To compare overall survival (OS) in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy 2. To compare mean change from baseline in health-related quality of life (HRQoL) scores from the European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy 3. To determine the safety and tolerability of pembrolizumab as adjuvant therapy in study participants | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) 2. Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30 3. Percentage of participants who experience an adverse event (AE) 4. Percentage of participants who discontinue study treatment due to an adverse event (AE) ; Timepoint(s) of evaluation of this end point: 1. Up to approximately 60 months for the evaluation of Overall Survival 2. Baseline and up to approximately 60 months for the evaluation of EORTC QLQ-C30 3. Up to approximately 63 months for the evaluation of adverse events 4. Up to approximately 38 months for the evaluation of discontinuations | — |
Countries
Argentina, Australia, Brazil, Canada, Colombia, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Norway, Portugal, Romania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed