Inclusion Criteria:
1. ≥ 18 years of age
2. Prior CDC-recommended vaccination series against PV, and has received a boost
immunization with PV Inactivated (IPOL®; Sanofi-Pasteur SA) at least 1 week, but less
than 6 weeks, prior to Day 1
a. Note: Patients who are unsure of their vaccination status must provide evidence of
anti-PV immunity prior to enrollment, as applicable
3. Biopsy proven (within 4 months of Day 1) unresectable cutaneous or mucosal melanoma
a. Note: Ocular melanoma is excluded.
4. Has disease that is accurately measurable by caliper or a radiological method
according to RECIST 1.1 criteria
5. At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion ≥10 mm in
longest diameter or, multiple injectable melanoma lesions which in aggregate have a
longest diameter of ≥10 mm
6. Had confirmed disease progression after receiving at least 6 weeks of treatment with
an FDA-approved anti-PD-1 therapy (as monotherapy or in combination), without
experiencing a toxicity requiring permanent discontinuation of the anti-PD-1. Patients
treated with anti-PD-1 in the adjuvant setting and who have confirmed progression
after at least 6 weeks of anti-PD-1 therapy are allowed.
a. NOTE: Patients with known BRAF mutation must have also failed or refused to receive
BRAF-targeted therapy (alone or in combination with MEK inhibitor) to be eligible.
7. Eastern Cooperative Oncology Group (ECOG) status of 0-1
8. Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN)
9. Adequate bone marrow, liver and renal function as assessed by the following:
1. Hemoglobin ≥ 9.0 g/dl, patients may be transfused
2. Lymphocyte count ≥ 0.5 x 10^9/L (500 µL)
3. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500 µL)
4. Platelet count ≥ 100 x 10^9/L (100,000 µL) without transfusion
5. AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN),
with the following exceptions: Patients with documented liver metastases: AST and
ALT ≤ 5 x ULN; Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
6. Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known
Gilbert disease: serum bilirubin level ≤ 3 x ULN
7. Estimated creatinine clearance < 30 ml/min, per MDRD equation
8. Serum albumin ≥ 25 g/L (2.5 g/dL)
9. For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤
1.5 x ULN
10. Life expectancy of >12 weeks
11. Signed informed consent form (ICF) indicating that participant understands the purpose
of, and procedures required for the study, and is willing/able to participate in the
study
Exclusion Criteria:
1. Symptomatic, untreated, or actively progressing CNS metastases. Participants with a
history of treated CNS lesions are eligible, provided the following criteria are met:
1. No stereotactic radiotherapy within 7 days, or whole-brain radiotherapy within 14
days of Day 1
2. No ongoing requirement for corticosteroids to manage CNS disease. Anticonvulsant
therapy at a stable dose is permitted.
3. Asymptomatic patients with CNS metastases newly detected at screening are
eligible for the study after receiving radiotherapy or surgery, with no need to
repeat the screening brain scan
2. History of leptomeningeal disease
3. Uncontrolled tumor-related pain. Participants requiring pain medication must be on a
stable regimen at study entry.
1. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or
metastases causing nerve impingement) should treated prior to enrollment.
Patients should be recovered from the effects of radiation. There is no required
minimum recovery period
2. Asymptomatic metastatic lesions that would likely cause functional deficits or
intractable pain with further growth (e.g., epidural metastasis that is not
currently associated with spinal cord compression) should be considered for
loco-regional therapy if appropriate prior to enrollment
4. Uncontrolled pleural effusion, pericardial effusion, or ascites a. Patients with
indwelling catheters (e.g., PleurX™) are allowed.
5. Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12
mg/dL or corrected serum calcium >ULN)
6. Active or history of autoimmune disease or immune deficiency within previous 2 years,
with the following exceptions:
1. History of autoimmune-related hypothyroidism that is managed by thyroid
replacement hormone
2. Type 1 diabetes mellitus that is well-controlled by an established insulin
regimen
3. Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations
only (e.g., patients with psoriatic arthritis are excluded), provided all of the
following conditions are met:
i. Rash must cover <10% of body surface area
ii. Disease is well-controlled at baseline and requires only low-potency topical
corticosteroids
iii. No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
calcineurin inhibitors, or high potency or oral corticosteroids within 12 months of
Day 1
7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis
on screening chest computed tomography (CT) scan
a. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
8. History of a Positive HIV RNA test (HIV 1 or 2 RNA by PCR)
9. Known active hepatitis B virus (HBV) infection (chronic or acute)
a. NOTE: Participants with a negative HBsAg test and a positive total hepatitis B core
antibody (HBcAb) test are allowed.
10. Known active hepatitis C virus (HCV) infection
a. NOTE: History of positive HCV antibody test, but negative HCV RNA test is allowed.
11. Active tuberculosis
12. Significant cardiovascular disease, such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3
months of Day 1, unstable arrhythmia, or unstable angina
13. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks (shorter interval for kinase inhibitors or other short half-life drugs
may be allowed with Sponsor approval) prior to treatment, or has not recovered from
all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2
neuropathy may be eligible.
a. Note: Anti-PD-1 within 4 weeks of Day 1 is allowed. If participant received major
surgery, they must have recovered adequately from the toxicity and/or complications
from the intervention prior to starting study treatment.
14. History of other malignancy within 2 years of Day 1, with the exception of those with
a negligible risk of metastasis or death (e.g., resected cutaneous basal cell
carcinoma, or other cancers with 5-year OS of >90%)
15. Severe infection within 4 weeks of Day 1, including, but not limited to,
hospitalization for complications of infection, bacteremia, or severe pneumonia
a. Prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic
obstructive pulmonary disease exacerbation) are allowed.
16. Prior allogeneic stem cell or solid organ transplantation
17. Treatment with a live, attenuated vaccine within 4 weeks of Day 1
18. Treatment with systemic immunosuppressive medication within 4 weeks of Day 1, with the
following exceptions:
1. Participants who received acute, low-dose systemic immunosuppressant medication
or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours
of corticosteroids for a contrast allergy) are eligible with Sponsor approval
2. Use of mineralocorticoids (e.g., fludrocortisone), or systemic prednisone
equivalent corticosteroid doses of <10mg per day are eligible for the study
3. Use of topical corticosteroids with occlusive dressings is prohibited
19. Known hypersensitivity to pembrolizumab, nivolumab or any of the respective excipients
20. A pregnant or nursing female, or women of child-bearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception starting from signed ICF through 150 days after last anti-PD-1 dose
21. History of human serum albumin allergy
22. History of neurological complications due to polio virus infection
23. History of agammaglobulinemia
24. History of worsening steroid myopathy (e.g., gradual progression of bilateral proximal
muscle weakness, and atrophy of proximal muscle groups)
25. Concurrent participation in a separate clinical trial during this study without
Sponsor approval
26. Any underlying medical condition for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (e.g., compromises
the well-being) or that could prevent, limit, or confound protocol-specified
assessments
