Inclusion Criteria:
1. ≥ 18 years of age
2. Prior CDC-recommended vaccination series against PV, and has received a boost
immunization with trivalent 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. Has biopsy proven unresectable cutaneous, acral or mucosal melanoma and is willing to
undergo tumor biopsy prior to the first dose of study drugs and at prespecified
intervals during the study (see Table 1).
1. Submission of an archival biopsy sample is allowed in lieu of the baseline tumor
biopsy, provided the tissue is ≤4 months old and the participant received no
intervening systemic/intratumoral anti-cancer therapy since the biopsy was
acquired.
2. Must have at least 1 lesion that is amenable to biopsy. The lesion must be safely
accessible as determined by the investigator and should not be located at sites
that require significant risk procedures to biopsy. Examples of sites considered
to be of significant risk include but are not limited to the following: the
brain, lung, mediastinum, pancreas, or endoscopic procedures extending beyond the
esophagus, stomach, or bowel wall.
4. Has ≥ 2 melanoma lesions that are accurately measurable by caliper or a radiological
method according to RECIST 1.1 criteria
1. One lesion must be injectable- defined as a visible or palpable 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
and where the minimum lesion size is ≥5 mm
2. Note that visceral lesions (eg, liver, lung, retroperitoneal, subpleural lesions)
are not considered injectable for the purposes of this trial.
5. Has confirmed disease progression per iRECIST after receiving at least 6 weeks of
treatment with an FDA-approved anti-PD-1/L1 therapy (as monotherapy or in combination)
without experiencing a toxicity requiring permanent discontinuation of the
anti-PD-1/L1. Patients treated with anti-PD-1/L1 in the adjuvant setting and who have
confirmed progression after at least 6 weeks of anti-PD-1/L1 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.
6. Eastern Cooperative Oncology Group (ECOG) status of 0-1
7. Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN)
8. 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. Measured or calculated (per institutional standards) creatinine clearance ≥ 30
ml/min (GRF can also be used in place of creatinine clearance)
8. For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤
1.5 x ULN
9. Life expectancy of >12 weeks
10. 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. Has biopsy-proven ocular melanoma
2. Symptomatic, untreated, or actively progressing central nervous system (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
3. History of leptomeningeal disease
4. 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
5. Uncontrolled pleural effusion, pericardial effusion, or ascites a. Patients with
indwelling catheters (e.g., PleurX™) are allowed.
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 a 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 or 5 elimination half-lives- whichever is shorter, prior to treatment,
or has not recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
Participants with ≤Grade 2 neuropathy are eligible
1. Note: Anti-PD-1/L1 within 4 weeks prior to Day 1 is allowed
2. 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
2. Patients receiving mineralocorticoids (e.g., fludrocortisone), or systemic
prednisone equivalent corticosteroid doses of <10mg per day are eligible for the
study
19. Known hypersensitivity to pembrolizumab, nivolumab, or any of the respective
excipients
20. Requires therapeutic anticoagulation and cannot discontinue anticoagulation safely
during the day prior, day of, and day after each PVSRIPO injection
a. NOTE: Participants receiving anticoagulation with warfarin at the time of study
entry are allowed if they can be transitioned to an alternative anticoagulant (eg, low
molecular weight heparin or direct oral anticoagulants) prior to the first dose of
PVSRIPO. Anyone transitioned from warfarin to an oral anticoagulant prior to the first
dose of PVSRIPO should have an INR <1.5x upper limit of normal in order to
participate. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered
anticoagulants for the purposes of this study (ie, are allowed)
21. 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
22. History of human serum albumin allergy
23. History of neurological complications due to polio virus infection
24. History of agammaglobulinemia
25. Concurrent participation in a separate interventional clinical trial during this
study.
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 participant's well-being) or that could prevent, limit, or confound
protocol-specified assessments
