| Eligibility |
Inclusion Criteria:
The subject must:
1. Be willing and able to provide written informed consent for the trial.
2. Be = 18 years of age on day of signing informed consent.
3. Have histologically confirmed diagnosis of unresectable Stage III or metastatic
melanoma.
- Patients may not have a diagnosis of uveal melanoma.
4. Have measurable disease based on RECIST 1.1.
5. Have a tumor sample (FFPE archival or newly obtained biopsy) of a metastatic site that
is available for biomarker analysis.
6. Have an ECOG of 0 or 1.
7. Demonstrate adequate organ function as below:
- Absolute neutrophil count (ANC) =1.5 x 109/L
- Platelets =100 x 109/L
- Hemoglobin =90 g/L (may be transfused)
- Serum creatinine OR CrCl = 1.5 X upper limit of normal (ULN) OR =60 mL/min for
subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for subjects with
total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) = 2.5 X ULN OR = 5 X ULN for subjects with liver
metastases
- Albumin >2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT)
- 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 =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
8. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
9. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.
10. Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy.
11. No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject:
1. Has had prior treatment for advanced unresectable or metastatic melanoma. Prior
treatment with BRAF and MEK inhibitors is permitted in this setting. A washout of at
least 5-half-lives (median terminal half-life) prior to the first dose of trial
treatment must have elapsed.
2. Has received prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2
agent.
3. Has evidence of symptomatic CNS lesions as determined by the investigator. Patients
with asymptomatic lesions or previously irradiated or surgically resected are
eligible.
4. Has a known additional malignancy that is progressing or requires active treatment.
5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg
daily prednisone equivalents) or any other form of immunosuppressive therapy within 7
days prior to the first dose of trial treatment. Inhaled or topical steroids, and
adrenal replacement doses = 10 mg prednisone equivalents are permitted.
6. Has = Grade 2 peripheral neuropathy.
7. Patients with an active autoimmune disease or a documented history of autoimmune
disease or syndrome that requires systemic steroids or immunosuppressive agents.
Patients with vitiligo or resolved childhood asthma/atopy is an exception to this
rule. Patients that require intermittent use of bronchodilators or local steroid
injections would not be excluded from the study. Patients with hypothyroidism stable
on hormone replacement will not be excluded from the study.
8. Has an active infection requiring systemic therapy.
9. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
10. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
11. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
12. Has a known history of active TB (Bacillus Tuberculosis)
13. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
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