|
The subject must have clinical stage IIB or IIC resectable MEL. Subjects may not have a diagnosis of uveal or mucosal melanoma |
|
|
|
|
|
Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial |
|
|
|
|
|
The subject must be ≥18 years of age on day of signing informed consent |
|
|
|
|
|
The subject must have a performance status of 0 or 1 on the ECOG Performance Scale |
|
|
|
|
The subject must demonstrate adequate organ function as defined in Table 1; all screening labs must be performed within 21 days of treatment initiation |
|
|
|
|
|
System Laboratory Value |
|
|
|
|
|
Hematologic |
|
|
|
|
|
ANC ≥1500/mcL |
|
|
|
|
|
Platelets ≥100,000/mcL |
|
|
|
|
|
Hemoglobin ≥9 g/dL or ≥5.6 mmol/L |
|
|
|
|
|
Renal |
|
|
|
|
|
Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR |
|
|
|
|
|
≥50 mL/min for subject with creatinine levels >1.5 X institutional ULN |
|
|
|
|
|
Hepatic |
|
|
|
|
|
Serum total bilirubin ≤1.5 X ULN OR |
|
|
|
|
|
Direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 ULN |
|
|
|
|
|
AST (SGOT) and ALT (SPGT) ≤2.5 X ULN OR ≤5 X ULN for subjects with liver metastases |
|
|
|
|
|
Coagulation |
|
|
|
|
|
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants |
|
|
|
|
|
Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants |
|
|
|
|
Female participants |
|
|
|
|
|
A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions |
|
|
|
|
|
applies |
|
|
|
|
|
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR |
|
|
|
|
|
A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and must be willing to use 2 methods of contraception or abstain from heterosexual intercourse for at least 2 weeks prior to the time of first dose of study medication through 120 days after the last dose of study medication |
|
|
|
|
Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication |
|
|
|
|
|
Female subjects of childbearing potential are defined as those women who have not been surgically sterilized or have not been free from menses for >1 year |
|
|
|
|
|
Male participants |
|
|
|
|
|
Male subjects must agree to follow the contraceptive guidance in Appendix 3 starting with the first dose of study medication, while on study, through 120 days after the last dose of study medication |
|
|
|
|
|
Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin
|
|
|
|
|
|
A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to first dose of study drug (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
|
|
|
|
|
|
Note: In the event that 72 hours have elapsed between the screening pregnancy test and the
|
|
|
|
|
|
first dose of study treatment, another pregnancy test (urine or serum) must be performed
|
|
|
|
|
|
and must be negative in order for subject to start receiving study medication
|
|
|
|
|
|
Has received prior therapy with an anti-PD-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
|
|
|
|
|
|
CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug
|
|
|
|
|
|
specifically targeting T-cell co-stimulation or checkpoint pathways
|
|
|
|
|
|
Has received prior systemic anti-cancer therapy including investigational agents
|
|
|
|
|
|
within 4 weeks Note: Participants must have recovered from all AEs due to previous
|
|
|
|
|
|
therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an
|
|
|
|
|
|
exception to this criterion
|
|
|
|
|
|
If participant received major surgery, they must have recovered adequately from the
|
|
|
|
|
|
toxicity and/or complications from the intervention prior to starting study treatment
|
|
|
|
|
|
Subject has received transfusion of blood products (including platelets or red blood
|
|
|
|
|
|
cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or
|
|
|
|
|
|
Has an active infection requiring systemic therapy
|
|
|
|
|
|
recombinant erythropoietin) within 4 weeks prior to study Day 1
|
|
|
|
|
|
Has received a live vaccine within 30 days prior to the first dose of study drug
|
|
|
|
|
|
Examples of live vaccines include, but are not limited to, the following: measles
|
|
|
|
|
|
Has a known history of active TB (Bacillus Tuberculosis)
|
|
|
|
|
|
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 (e.g., FluMist®) are live attenuated vaccines and are not allowed
|
|
|
|
|
|
Is currently participating in or has participated in a study of an investigational
|
|
|
|
|
|
Has hepatic decompensation (Child-Pugh score >6 [class B and C])
|
|
|
|
|
|
agent or has used an investigational device within 4 weeks prior to the first dose of
|
|
|
|
|
|
Has uncontrolled thyroid dysfunction
|
|
|
|
|
|
study treatment
|
|
|
|
|
|
Has uncontrolled diabetes mellitus
|
|
|
|
|
|
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
|
|
|
|
|
|
Has a known additional malignancy that is progressing or requires active treatment
|
|
|
|
|
|
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
|
|
|
|
|
|
the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that
|
|
|
|
|
|
have undergone potentially curative therapy are not excluded
|
|
|
|
|
|
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
|
|
|
|
|
|
Has active autoimmune disease that has required systemic treatment in the past 3
|
|
|
|
|
|
months (i.e. with use of disease modifying agents, corticosteroids or
|
|
|
|
|
|
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
|
|
|
|
|
|
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency
|
|
|
|
|
|
etc.) is not considered a form of systemic treatment
|
|
|
|
|
|
Has evidence of active interstitial lung disease or a history of (non-infectious)
|
|
|
|
|
|
pneumonitis that required steroids or has current pneumonitis
|
|
|
|
|
|
Has a known history of Human Immunodeficiency Virus (HIV). (HIV 1/2 antibodies) as
|
|
|
|
|
|
determined by medical record review
|
|
|
|
|
|
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
|
|
|
|
|
|
reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection
|
|
|
|
|
|
as determined by medical record review
|
|
|
|
|
|
Has a history or current evidence of any condition, therapy, or laboratory abnormality
|
|
|
|
|
|
that might confound the results of the study, interfere with the subject's
|
|
|
|
|
|
participation for the full duration of the study, or is not in the best interest of
|
|
|
|
|
|
the subject to participate, in the opinion of the treating investigator
|
|
|
|
|
|
Has known psychiatric or substance abuse disorders that would interfere with
|
|
|
|
|
|
cooperation with the requirements of the trial
|
|
|
|
|
|
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 trial treatment
|
|
|
|
|
|
Has severe cardiovascular disease, i.e. arrhythmias, requiring chronic treatment
|
|
|
|
|
|
congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease
|
|
|
|