Stage III melanoma (AJCC R0) with histologically confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC, 2010): Stage IIIA with metastasis > 1 mm
Conditions
Sponsors
Merck Sharp & Dohme LLC, a Subsidiary of Merck & Co. Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - At least 18 years of age. - Complete resection of Stage III melanoma (AJCC R0) with histologically confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC, 2010): Stage IIIA with metastasis > 1 mm; any Stage IIIB or IIIC. No past or current in-transit metastases or satellitosis. - Melanoma with unknown origin of the primary is eligible - Mandatory to ship tumor sample for evaluation of PD-L1 expression. - The maximum duration from surgery to first study drug treatment is 13 weeks. Treatment should start only after complete wound healing from the surgery. Note: if there is a delay of 1-7 days exceeding 13 weeks due to extreme unforeseen circumstances, the eligibility should be discussed with the medical monitor. - Disease status for the post-surgery baseline assessment must be documented by full Chest/Abdomen/Pelvis CT and/or MRI with Neck CT and/or MRI (for Head and Neck primaries) and complete clinical examination after the informed consent and prior to enrollment. Note: if a patient had laboratory/imaging tests as part of local routine guidelines (standard of care) prior to signing informed consent, the procedures will be acceptable for screening purposes if they are within the window required by the protocol. - Disease-free (no loco-regional relapse or distant metastasis); no clinical evidence for brain metastases. - BRAF mutation status (known or not done). - ECOG performance status of 0 or 1. - Patient demonstrates adequate organ function as defined in the protocol - Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. - WOCBP should use adequate birth control methods. - Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last dose of study drug . - Patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ. Please refer to the Diagnosis and Main Criteria for Inclusion in the Protocol for the full list of inclusion criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 738 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 162
Exclusion criteria
Exclusion criteria: - Mucosal or ocular melanoma. - Prior therapy for melanoma except surgery for primary melanoma lesions. - history of (non-infectious) pneumonitis that required steroids or current pneumonitis. History of or current interstitial lung disease. - history of another malignancy or a concurrent malignancy. Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ. - active autoimmune disease that has required systemic treatment in past 2 years (i.e. 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, etc.) is not considered a form of systemic treatment. - active infection requiring therapy. - diagnosis of immunodeficiency, no systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment - known history of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C. - treatment with live vaccines within 30 days prior to the first dose of study medication are not eligible. - prior treatment with any anti-CTLA4 monoclonal antibody or anti-PD-1, or PD-L1 or PD-L2 agent. - Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to the first dose of treatment - patient is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject. - female patients who are Breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To prospectively assess whether post-operative adjuvant therapy with pembrolizumab improves recurrence-free survival, as compared to placebo in high-risk patients with complete resection of Stage IIIA (>1 mm metastasis), IIIB and IIIC melanoma. - To prospectively assess whether in the subgroup of patients with PD-L1-positive tumor expression, pembrolizumab improves recurrence-free survival as compared to placebo. ;Secondary Objective: - To prospectively assess whether post-operative adjuvant therapy with pembrolizumab improves distant metastasis free survival as compared to placebo. - To prospectively assess whether in the subgroup of patients with PD-L1-positive tumor expression pembrolizumab improves distant metastasis free survival as compared to placebo. - To prospectively assess whether post-operative adjuvant therapy with pembrolizumab improves overall survival, as compared to placebo. - To prospectively assess whether in the subgroup of patients with PD-L1-positive tumor expression pembrolizumab improves overall survival as compared to placebo. - To compare adverse event profiles (AE and Serious Adverse Event (SAE)) between patients receiving pembrolizumab versus patients in the placebo arm. - To evaluate the pharmacokinetics (PK) of pembrolizumab when pembrolizumab is administered at 200 mg every three weeks. ;Primary end point(s): 1. Recurrence free survival (RFS) 2. RFS in subgroup of patients with PD-L1-positive tumor expression receiving either pembrolizumab or placebo ;Timepoint(s) of evaluation of this end point: 1. Every 12 weeks during treatment and for the first two years. From year 3 to 5, every 6 months and yearly thereafter. 2. Every 12 weeks during treatment and for the first two years. From year 3 to 5, every 6 months and yearly thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Distant metastases-free survival (DMFS) 2. DMFS in subgroup of patients with PD-L1-positive tumor expression receiving either pembrolizumab or placebo 3. Overall survival (OS) 4. OS in subgroup of patients with PD-L1-positive tumor expression receiving either pembrolizumab or placebo 5. Toxicity profile according to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 6. To evaluate the pharmacokinetics (PK) of pembrolizumab when pembrolizumab is administered 200 mg every 3 weeks 7. To assess for development of anti-drug antibodies (ADA);Timepoint(s) of evaluation of this end point: 1. Every 12 weeks during treatment and for the first two years. From year 3 to 5, every 6 months and yearly thereafter. 2. Every 12 weeks during treatment and for the first two years. From year 3 to 5, every 6 months and yearly thereafter. 3. OS will be measured from the date of randomization until the date of death. 4. OS will be measured from the date of randomization until the date of death. 5. Every 6 weeks during treatment and at 12 weeks after the last treatment 6. Prior to treatment start (before injection 1), week 4 (before injection N°2), week 10 (before injection N°4 ), week 22 (before injection N°8 ) and at 12 months (before injection 16). At 30 days after the last treatment 7. Prior to treatment start, weeks 4, 10, 22 and at 12 months. At 30 days after the last treatment | — |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Serbia, Singapore, Slovenia, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc
Outcome results
None listed