Ensayos clínicos

Inclusion Criteria:

1. Signed written informed consent.

2. Males or females aged 18 years and older.

3. Performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.

4. For subject in Cohort 2: cytologically confirmed advanced/metastatic or surgically
unresectable HCC, with documented disease progression after at least two lines of FDA
approved systemic therapy, including immunotherapy or anti-angiogenesis therapy as the
first line treatment and at least one regimen of the following agents as the second
line: anti-angiogenesis agents, tyrosine kinase inhibitors or immunotherapy.

5. For subject in Cohort 3: Histologically or cytologically confirmed advanced/metastatic
or surgically unresectable ICC, with documented disease progression after chemotherapy
as the first line systemic therapy. For patients with known IDH1 mutation, they must
receive the appropriate targeted therapy with a IDH1 inhibitor and for patients with
MSI-H tumors, they must receive immunotherapy with PD-1 inhibitors.

6. For subjects in Cohort 1: should fulfill either inclusion criteria 4) or 5).

7. Liver function: Child-Pugh A-B for cohort 1 and 2.

8. At least 1 injectable target lesion ≥ 15 mm in longest diameter and/or nodal lesions
that are visible or palpable deemed injectable as per Principal Investigator's (PI's)
discretion and if approved by the Contract Research Organization (CRO) Medical Monitor
and the Sponsor. Subjects with hepatic lesions, superficial metastatic lesions or
non-subcutaneous lymph nodes can be considered for IT injection with Investigational
product (IP)*.

Exclusion Criteria:

1. Participation in any trial of any other investigational agent within the last 4 weeks
prior to dosing. Wash out periods to be reviewed on a case by case basis with Medical
Monitor, as required.

2. Tumors to be injected lying in mucosal regions or close to an airway, major blood
vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion
or compression in the case of tumor swelling or erosion into a major vessel in the
case of necrosis.

3. Subjects with any primary Central Nervous System (CNS) malignancy including glioma and
current, active, progressing CNS malignancy, including carcinomatosis meningitis are
excluded. Subjects with treated brain metastases are eligible if there is no evidence
of progression for at least 4 weeks after CNS-directed treatment, as ascertained by
clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed
tomography [CT] scan) during the screening period and off steroids (for at least 2
weeks prior to first dose of IP).

4. Major surgery within 14 days prior to dosing.

5. Intercurrent serious infections within 28 days prior to Screening or treated
systematically with antibiotics within 14 days prior to signing ICF.

6. Life-threatening illness unrelated to cancer.

7. Active Herpes infection.

8. Treatment with antiviral agents within 14 days prior to dosing.

9. Uncontrolled congestive heart failure.

10. Known to test positive for human immunodeficiency virus (HIV) or syphilis.

11.  Active infection including hepatitis B (HBV) or hepatitis C (HCV) that currently
under anti-virus treatment which can affect study drug treatment as per investigator's
decision.

12. Use of ganciclovir or acyclovir within 14 days prior to dosing.

13. Subjects with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days prior to dosing. Inhaled or topical steroids, and adrenal replacement steroid
doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease.

14. Subjects who have been on systemic anticoagulants within 14 days prior to dosing
and/or with International Normalized Ratio (INR) > 1.5 x the upper limit of the
reference range are excluded from this study.

15. Subjects with prior radiation therapy to the tumor lesion to be injected are excluded
from the study, unless there is evidence of tumor progression in the most recent
imaging, following completion of radiotherapy.