- - All subjects must be either Stage IIIb/c or Stage IV AJCC (7th edition) and have
histologically confirmed melanoma that is completely surgically resected in order to
Subjects must have been surgically rendered free of disease with negative
margins on resected specimens. Please refer to Appendix 1 or description of AJCC 7th
editions of TNM and staging.
- - If Stage III melanoma (whether Stage IIIb or IIIc) the subjects must have clinically
detectable lymph nodes that are confirmed as malignant on the pathology report
Clinically detectable lymph nodes are defined as:
- A palpable node (confirmed as malignant by pathology)
- A non-palpable but enlarged lymph node by CT (at least 15 mm in short axis) and
confirmed as malignant by pathology
- A PET positive lymph node of any size confirmed by pathology
- Evidence of pathologically macrometastatic disease in one or more lymph nodes
defined by one or more foci of melanoma at least 1cm in diameter
- All melanomas, except ocular/uveal melanoma, regardless of primary site of
disease will be allowed
- Complete resection of Stage III disease that is documented on the surgical
and pathology reports or complete resection of Stage IV disease with margins
negative that is documented on the pathology report.
- - Complete resection must be performed within 16 weeks prior to recruitment
- Subjects must not have received systemic medical anti-cancer treatment
(postsurgical local/locoregional radiation therapy applied according to
local standard practice is allowed)
- All subjects must have disease-free status documented by a complete physical
examination and total body PET/CT imaging within 4 weeks prior to
- - ECOG performance status score of 0 or 1 (Appendix 2)
- In order to be recruited, tumor tissue from the resected site of disease
must be provided for biomarker analyses.
If insufficient tumor tissue
content is provided for analysis, acquisition of additional archived tumor
tissue (block and /or slides) for the biomarker analysis is required.
- - Prior treated central nervous system (CNS) metastases must be without MRI
evidence of recurrence for at least 4 weeks after treatment, subjects must
be off immunosuppressive doses of systemic steroids (> 10 mg/day or
equivalent) for at least 14 days prior to study drug administration, and
must have returned to neurologic baseline post-operatively.
period of stability is measured after the completion of the neurologic
interventions, ie surgery and/or radiation
- - In addition to neurosurgery to treat CNS metastases, adjuvant radiation
after the resection of CNS metastasis is allowed.
Immunosuppressive doses of
systemic steroids (doses < 10 mg/day prednisone or equivalent) must be
discontinued at least 14 days before study drug administration
- - Prior surgery that required general anesthesia must be completed at least 4
weeks before study drug administration.
Surgery requiring local/epidural
anesthesia must be completed at least 72 hours before study drug
- - All baseline laboratory requirements will be assessed and should be obtained
within 14 days of recruitment.
Screening laboratory values must meet the
i. WBCs > 2000/μL ii. Neutrophils > 1500/μL iii. Lymphocytes > 1000/μL iv.
Platelets > 100 x 10³/μL v. Hemoglobin > 9.0 g/dL vi. Creatinine Serum
creatinine <1.5 x upper limit of normal (ULN) or creatinine clearance > 40
mL/minute (using Cockcroft/Gault formula) vii. AST < ULN viii. ALT < ULN ix.
Total Bilirubin < 1 x ULN (except subjects with Gilbert Syndrome who must
have total bilirubin < 3.0 mg/dL) x. LDH < 1,5x ULN xi. CRP < 2x ULN
- - Subjects with leptomeningeal metastases
- History of ocular/uveal melanoma
- Medical History and Concurrent Diseases
- Subjects with previous non-melanoma malignancies are excluded unless a complete
remission was achieved at least 3 years prior to study entry and no additional
therapy is required or anticipated to be required during the study period
(exceptions include but are not limited to, non-melanoma skin cancers; in situ
bladder cancer, in situ gastric cancer, or in situ colon cancers; in situ
cervical cancers/dysplasia; or breast carcinoma in situ)
- Subjects with active, known, or suspected autoimmune disease.
Subjects with type
I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment are permitted to enroll. For any cases
of uncertainty, it is recommended that a BMS medical monitor be consulted prior
to signing informed consent.
- - Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of study drug administration.
Inhaled or topical
steroids are permitted in the absence of active autoimmune disease.
- - Prior therapy for melanoma except surgery for the melanoma lesion(s) and except
adjuvant RT after neurosurgical resection for CNS lesions.
who received prior therapy with interferon, anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody
or drug specifically targeting T cell co-stimulation or checkpoint pathways) are
- - Treatment directed against the resected melanoma (eg, chemotherapy, targeted
agents, biotherapy, or limb perfusion) that is administered after the complete
- - Any serious or uncontrolled medical disorder or active infection that, in the
opinion of the investigator, may increase the risk associated with study
participation, study drug administration, or would impair the ability of the
subject to receive protocol therapy.
- - Physical and Laboratory Test Findings
- Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus
ribonucleic acid (HCV RNA) indicating acute or chronic infection.
- - Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
- Allergies and Adverse Drug Reaction
- History of Grade ≥3 allergy to humanized monoclonal antibodies
- Other Exclusion Criteria
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness
- Pregnant or nursing women
- Psychological, familial, sociological, or geographical conditions that
potentially hamper compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the subject before registration in the