A patient will be ineligible for study participation if any of the following criteria are met:
1. Patients with severe hypersensitivity or a history of any hypersensitivity to the similar drug class of the study drugs (IP and Pembrolizumab).
2. Patients with tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, unless there is demonstrated progression in the lesion as per the Investigator’s assessment.
3. Patients with tumour lesions with macroscopic intravascular tumour invasion (e.g. liver lesions with tumour infiltration into the main portal vein, hepatic vein or vena cava).
4. Patients with any of the following medical histories or surgery/procedure histories:
a. Major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to baseline (within 2 weeks for video-assisted thoracoscopic surgery or open-and-closed surgery)
b. Severe cardiovascular disease within 24 weeks prior to baseline
c. Severe cerebrovascular disease within 24 weeks prior to baseline
d. Pulmonary thromboembolism, deep vein thrombosis (DVT) or other clinically significantly severe lung disease within 24 weeks prior to baseline
e. History of organ transplant that requires use of immunosuppressive medications
5. Patients who have any of the following concomitant diseases at baseline:
a. History of malignancies other than melanoma, gastric adenocarcinoma or gastro-oesophageal junction adenocarcinoma or gastrointestinal stromal tumours or solid tumours of colon or lung within 5 years
b. Clinically significant symptom or uncontrolled central nervous system or brain metastases. Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening period and off steroids (for at least 2 weeks prior to first dose of IP).
c. History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy or evidence of clinically significant immunosuppression. Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
d. Class III or IV heart failure by New York Heart Association classification
e. Uncontrolled hypertension (SBP/ DBP greater than 160/100 mmHg)
f. Active hepatitis B and hepatitis C virus infection
g. Known infection with human immunodeficiency virus
h. History of primary immune deficiency
i. Other active viral infections
j. Thromboembolic disease or bleeding diatheses
k. Severe infection or other uncontrolled active infectious disease requiring antibiotics or antiviral agents that would interfere with the evaluation of safety and efficacy in the judgment of the Investigator.
6. Patients who have received any of the following medications:
a. Administration of granulocyte colony-stimulating factor or platelet transfusion within 2 weeks prior to baseline for correction of ANC or platelet count
b. Patients with therapeutic doses of anticoagulants, should be excluded from most deep lesion biopsies and injections. However, for deep injections in patients receiving a preventive dose of LMW heparin it is recommended that their LMW heparin treatment is stopped 24 hours before the intratumoral injection and resumed 24 hours after the injection.
c. Patients with current or prior use of immunosuppressive medication within 14 days before the first dose of IP. The following are exceptions to this criterion:
i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection)
ii. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. Inhaled or topical steroids, and adrenal replacement steroid doses less than or equal to 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Inhaled or topical steroids, and adrenal replacement steroid doses less than or equal to 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
iii. Steroids as premedication for hypersensitivity reactions (e.g. computerized tomography [CT] scan premedication)
iv. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
v. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.
7. Patients who have received other IP or investigational device within 4 weeks prior to baseline.
8. Patients with any prior Grade 3 or higher immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved Grade >1 irAE (as per NCI-CTCAE version 5.0)
9. Patients with any Grade greater than 1 toxicity (as per NCI-CTCAE version 5.0) related to prior anti-cancer therapy, except those that are deemed not clinically significant by the Investigator in discussion with the study medical monitor, sponsor’s CMO.
10. Patients who, in the opinion of the Investigator, are unsuitable or unable to participate in the study.