A Phase 1 Study of OTS-412 (Recombinant Oncolytic Vaccinia Virus) in Treatment-refractory Solid Tumor Patients

Exclusion Criteria

• •1. Patients who have previously received talimogene laherparepvec (Imlygic) or any other oncolytic virus, have received any systemic or local anti-cancer therapy for tumors within 4 weeks prior to the first administration of the study drugs(C1D1), or have not recovered from the adverse events due to these therapies to at least Grade 1 severity or returned to baseline levels prior to C1D1, with the exceptions of any grade of alopecia and Grade 2 neuropathy.
• •2. Patients who have untreated symptomatic brain metastases, have treated brain metastases without evidence of stability or improvement on two scans at least two weeks apart, have leptomeningeal disease regardless of treatment, or have received anti-convulsants within the last 28 days.
• •3. Tumors adjacent to vital neurovascular structures or at risk of airway compromise in the event of post injection tumor swelling, bleeding, or inflammation. Patients with tumors near vital structures can be enrolled as long as they have other lesions that are appropriate for injection (these tumors near vital structures will not be injected).
• •4. History of other malignancies that developed within 5 years (However, cervical carcinoma in situ, basal cell carcinoma, or squamous cell skin cancer, and all cancers after 5 years since it was cured are acceptable.)
• •5. History of organ transplant surgery
• •6. Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose systemic corticosteroids (prednisone 20 mg/day or equivalent which is ongoing and/or was taken more than 4 weeks within the preceding 2 months of study treatment)
• •7. History of or active autoimmune disease
• •8. Ongoing severe inflammatory skin disease (as determined by the Investigator) requiring medical treatment or history of severe eczema (as determined by the Investigator) requiring prior medical treatment
• •9. Anticoagulation or anti-platelet medication that cannot be withheld for the required period prior to and after the OTS-412 injection, specifically:
• •* Coumadin for 7 days
• •* Direct Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban) for 4 days
• •* Oral direct thrombin inhibitor (dabigatran) for 4 days
• •* Aspirin, clopidogrel, ticagrelor for 7 days
• •* Prasugrel for 9 days
• •* Low molecular weight heparin for 24 hours
• •* Unfractionated heparin for 12 hours Please contact the Sponsor for questions regarding the management of other antithrombotic agents prior to treatment.
• •10. Taking antiviral drugs (immunoglobulin, interferon, etc.) or being unable to discontinue these medications at least 7 days prior to receiving the study drugs (note that oral antiviral drugs for hepatitis B and C are allowed).
• •11. Severe medical conditions, as determined by the Investigator, that may increase the patient's susceptibility to adverse medical risks during or after OTS-412 treatment, such as volume loading, tachycardia, or hypotension.
• •12. Current or history of significant cardiovascular disease, including significant coronary artery disease (e.g., requiring angioplasty or stent), congestive heart failure within the preceding 12 months, myocardial infarction, ischemic cardiomyopathy, or myocarditis, unless cardiology consultation and clearance have been obtained for study participation
• •13. History of the side effects of past smallpox vaccinations
• •14. History of the hypersensitivity or severe/serious AEs to the components of the study drugs
• •15. Unable to receiving a contrast medium for a radiological scan due to a history of allergy to iodide contrast agents
• •16. Vaccination with live vaccines within 4 weeks before the first administration of the study drugs
• •17. Receiving an investigational product within 4 weeks prior to the first administration of the study drugs
• •18. Pregnant or breastfeeding women
• •19. Patient who does not consent to the use of appropriate contraceptive methods for at least 6 months, when the woman is of childbearing age, or at least 1 year, when the male patient's spouse is a woman of childbearing age, after the last administration of the study drugs
• •20. Other medical condition that in the judgement of the Investigator may increase the risk associated with study participation or may interfere with interpretation of study results and/or otherwise make the patient inappropriate for study participation
• •21. Patient unable or unwilling to comply with the protocol