- Histologic diagnosis of unresectable III or stage IV metastatic melanoma.
- Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is
measurable radiographically (based on RECIST 1.1).
- No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease.
- ECOG performance status of 0-1.
- Life expectancy ≥ 4 months.
- Screening laboratory parameters:
- White blood cell (WBC) count ≥ 2000/μL;
- Absolute neutrophil count (ANC) ≥ 1500/μL;
- Platelets ≥ 100,000/μL;
- Hemoglobin (Hgb) ≥ 9 g/dL;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper
limit of normal (ULN);
- Total bilirubin ≤ 1.5 × ULN (< 3 mg/dL for subjects with Gilbert's disease);
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using
the Cockcroft-Gault formula below): Female CrCl = [(140 - age in years) x weight
in kg x 0.85] / [72 x serum creatinine in mg/dL] Male CrCl = [(140 - age in
years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL]
- Age ≥ 18 years.
- Females of childbearing potential who are sexually active with a nonsterilized male
partner must use 2 methods of effective contraception from screening, and must agree
to continue using such precautions for 23 weeks after the final dose of
investigational product; cessation of birth control after this point should be
discussed with a responsible physician. Periodic abstinence, the rhythm method, and
the withdrawal method are not acceptable methods of birth control.
[Females of childbearing potential are defined as those who are not surgically sterile
(i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or
postmenopausal (defined as 12 months with no menses without an alternative medical cause).]
Nonsterilized males who are sexually active with a female partner of childbearing potential
must use 2 acceptable methods of effective contraception from Day 1 and for 31 weeks after
receipt of the final dose of investigational product.
Acceptable methods of effective contraception are described in the following table:
- Barrier Methods - Male condom plus spermicide, cap plus spermicide, or diaphragm plus
- Intrauterine Device Methods-Copper T, or Levonorgestrel-releasing intrauterine system
(e.g., Mirena®), also considered a hormonal method.
- Hormonal Methods-Implants, hormone shot or injection, combined pill, minipilimumabll,
- Active autoimmune disease or any condition requiring systemic treatment with either
corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive
medications within 14 days of study drug administration. Inhaled or topical steroids
and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in
the absence of active autoimmune disease.
- History of motor neuropathy considered to be of autoimmune origin (e.g.,
Guillain-Barre Syndrome, Myasthenia Gravis).
- Other active, concurrent malignancy that requires ongoing systemic treatment or
interferes with radiographic assessment of melanoma response as determined by the
- Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C infection. Antibody to
Hepatitis B or C without evidence of active infection may be allowed.
- History of severe allergic reactions to any unknown allergens or any components of the
- Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
- Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.
- Lack of availability for immunological and clinical assessments or post-study
follow-up contact to determine relapse and survival.
- Women who are breastfeeding or who are pregnant as evidenced by a positive serum
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed
within 14 days of the first dose of study drug and by a urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of the first dose of
- Any condition that, in the clinical judgment of the treating physician, is likely to
prevent the subject from complying with any aspect of the protocol or that may put the
subject at unacceptable risk.