Intravenous T3011 Given as a Single Agent and in Combination With Other Therapy in Subjects With Advanced Solid Tumors

Exclusion Criteria

• •Subjects are to be excluded from the study if they meet any of the following criteria:
• •1. Prior treatment with another OV (including T-VEC), tumor vaccines, cellular therapy or gene therapy.
• •2. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.
• •3. Subjects with rapidly disease progression, defined as subjects who cannot tolerate interruption of systemic antitumor therapy for at least 8 weeks, according to the investigator's judgment.
• •4. Previous intolerance to anti-PD-(L)1 monoclonal antibody or previous history of immunotherapy induced non-infectious pneumonitis/interstitial lung disease.
• •5. Requires continued concurrent systemic therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). Topical use of drugs against HSV are allowed.
• •6. Live, attenuated vaccines within 4 weeks prior to initiation of study treatment (subjects vaccinated with inactivated vaccines can be enrolled).
• •7. Primary or acquired immunodeficient states (leukemia, lymphoma, human immunodeficiency virus \[HIV\]/acquired immunodeficiency syndrome \[AIDS\]).
• •8. Active infection requiring systemic treatment.
• •9. Pregnant or lactating.
• •10. Splenectomy, previous allogenic tissue/solid organ transplant.
• •11. Positive serological test of hepatitis B virus (HBV) or hepatitis C virus at Screening.
• •* Subjects who test positive for anti-hepatitis C antibody (anti-HCV) but negative for HCV ribonucleic acid (RNA) are considered eligible to participate in the study.
• •* Subjects with infection of hepatitis B (positive hepatitis B surface antigen \[HBsAg\] result) will be excluded. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible.
• •12. Active autoimmune disease or other medical conditions (e.g., active interstitial lung disease/pneumonitis or eczema, psoriasis, or other clinically significant dermatologic disorders) requiring chronic systemic steroid (\> 10 mg/day prednisone or equivalent) or immunosuppressive therapy within 4 weeks prior to first administration of study treatment (unless agreed otherwise between the Medical Monitor and the Investigator on a case-by-case basis). Non-systemic corticosteroids (eg, topical, inhaled) are allowed.
• •13. Subjects with untreated and/or symptomatic metastatic central nervous system (CNS) disease, primary CNS tumors, leptomeningeal disease or spinal cord compression. However, subjects with brain/CNS metastases who have undergone surgery or radiotherapy, whose disease is stable and who have been on a stable dose of corticosteroids (≤ 10 mg prednisone or equivalent) for at least 4 weeks prior to the first administration of study treatment will be eligible.
• •14. History of another primary malignant tumor, except the following: 1) the patient has undergone potentially curative therapy with no evidence of that disease and recurrence for 3 years prior to the first dose of study treatment; 2) Adequately treated non-melanoma skin cancer or lentigo with no evidence of malignancy; 3) Adequately treated carcinoma in situ without evidence of disease.
• •15. Subjects with moderate to large amount of pleural effusion, ascites or pericardial effusion who need drug or medical intervention. Subject may be eligible to participate following discussion with investigator and approval from the sponsor.
• •16. Unexplained \>38.5℃ fever (If the fever is caused by the tumor according to the investigator's judgment, the patient can be enrolled) occurs during the screening period or on the day of administration, which in the judgment of investigator, would interfere with patient participation in the study or evaluation of patient's efficacy.
• •17. History of seizure disorders within 6 months prior to Screening.
• •18. Active oral or skin herpes lesion at Screening.
• •19. Plan to receive any other anti-tumor therapy (including herbal therapy that has anti-tumor effects) during treatment with study drug.
• •20. History of congestive heart failure (\> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest), or clinically significant cardiac arrhythmias.
• •21. History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody or their excipients.
• •22. History of psychiatric disorders that would interfere with cooperation with the requirements of the trial or is still requiring for medication control.
• •23. History of substance abuse (including alcohol) within 6 months prior to signing informed consent.
• •24. Other systemic conditions or organ abnormalities that, in the opinion of the Investigator, may interfere with the conduct and/or interpretation of the current study.