- Adults 18 years of age or older.
- Histopathologically confirmed melanoma with an injectable cutaneous or lymph node
metastasis that has progressed in the opinion of the treating investigator despite
administering a Food and Drug Administration (FDA) approved anti-PD1 agent, with or
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
- Measurable disease according to RECIST 1.1.
- Acceptable coagulation status: international normalised ratio (INR) of blood clotting,
prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit
of normal (ULN).
- Completion of local therapy, such as radiation, surgical resection, injectable
immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of
- Adverse events from previous cancer therapies (excluding alopecia) must have recovered
to grade 1 (CTCAE, most recent version). Stable grade 2 AEs such as endocrine
conditions are allowed, and other chronic stable AEs may be considered on a case by
case basis by the Principal Investigator.
- Clinical stability of brain metastases for at least 4 weeks prior to first day of
- Acceptable liver and renal functions defined as:
- Total bilirubin ≤1.5 x ULN (does not include patients with Gilbert's Disease)
- Aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) ≤3.0
- Serum creatinine ≤1.5 x ULN
- Acceptable haematological function defined as (Patients can be transfused to meet the
haemoglobin entry criteria):
- Haemoglobin ≥9 g/dL
- Neutrophils ≥1.5 x 10^9/L
- Platelet count ≥75 x 10^9/L
- Able to provide valid written informed consent.
- All women of childbearing potential must have a negative urine or serum pregnancy test
- All patients must agree to use barrier contraception (i.e. condom) during study
treatment and for 2 months after the last virus treatment and 4 months after the last
dose of chemotherapy and pembrolizumab.
- A concomitant medical condition requiring receipt of a therapeutic anticoagulant that
in the opinion of the treating physician cannot safely allow for therapeutic injection
of ONCOS-102 and tumor biopsies. Local clinical practice can be followed with regard
to holding a therapeutic anticoagulant during invasive procedures such as biopsies.
- A concomitant medical condition that in the opinion of the treating physician would
pose unreasonable additional risk to therapeutic injection of ONCOS-102.
- Receipt of Investigational agents within 28 days prior to first dose of protocol
- Any symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease,
ulcerative colitis) that requires administration of >10mg of prednisone equivalent.
Lower dose steroids for conditions such as hypophysitis are allowed.
- Any prior severe adverse event attributed to prior anti-PD1 therapy that, in the
Principal investigator's opinion, would contraindicate pembrolizumab administration
- Grade 2 or higher pneumonitis
- Grade 4 AST or ALT elevation
- Grade 3 or higher colitis attributable to PD1 blockade; note that colitis
attributable to ipilimumab is not excluded
- Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase
or lipase are not contraindications to therapy on this trial
- Known active infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV.
Cleared HBV/HCV infection is not an exclusion, nor is HIV infection with cluster of
differentiations 4 (CD4) counts >500 and an undetectable viral load.
- Active bacterial, viral, or fungal infections, requiring systemic therapy apart from
anti-viral maintenance therapy for HIV.
- History of organ transplant.
- Patients requiring chronic systemic immunosuppressants, including steroids (prednisone
daily equivalent of >10 mg).
- Brain metastases that are clinically unstable (e.g. showing unequivocal growth on
imaging, requiring radiation therapy, or steroids >10mg of prednisone equivalent)
within 4 weeks of first dose of study drug.
- Known severe congenital or acquired cellular or humoral immunodeficiency such as
common variable immunodeficiency.
- Women who are pregnant or breast-feeding currently or are planning to conceive during
or up to 4 months after end of protocol therapy.