Oncolytic Virotherapy Plus PD-1 Inhibitor for Patients With Refractory Malignant Ascites

Inclusion Criteria:

• Written informed consent obtained.
• Age ≥ 18 years at time of study entry.
• Pathologically diagnosed solid tumor malignancy.
• Malignant peritoneal ascites confirmed by peritoneal brush cytology.
• Failures from chemotherapy against malignant ascites.
• Cooperative Oncology Group-Status (ECOG Status) 0 or 1

Exclusion Criteria:

• Previous (<4 weeks) or concurrent treatment with systemic or intraperitonealchemotherapy or biological agents such as monoclonal antibodies.
• History of cardiac disease, including clinically significant gastrointestinal bleedingwithin 4 weeks prior to start of study treatment
• Thrombotic or embolic events such as cerebrovascular accident (including transientischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 monthsPrior to the first dose of study drug with the exception of thrombosis of a segmentalportal vein.
• Prior treatment with oncolytic virotherapy.
• Radiotherapy administered less then 4 weeks prior to study treatment start.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have notrecovered from effects of major surgery.
• Patients with second primary cancer, except adequately treated basal skin cancer orcarcinoma in-situ of the cervix.
• Immunocompromised patients, e.g. patients who are known to be serologically positivefor human immunodeficiency virus (HIV).
• Participation in another clinical study with an investigational product during thelast 30 days before inclusion or 7 half-lifes of previously used trial medication,whichever is longer.
• Any condition or comorbidity that, in the opinion of the investigator, would interferewith evaluation of study Treatment or interpretation of patient safety or studyresults, including but not limited to:
• history of interstitial lung disease
• Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
• known acute or chronic pancreatitis
• active tuberculosis
• any other active infection (viral, fungal or bacterial) requiring systemic therapy
• history of allogeneic tissue/solid organ transplant
• diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days prior to the first doseof Tislelizumab treatment.
• Has an active autoimmune disease requiring systemic treatment within the past 3 monthsor a documented history of clinically severe autoimmune disease, or a syndrome thatrequires systemic steroids or immunosuppressive agents. Exceptions: Subjects withvitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopyare an exception to this rule. Subjects that require intermittent use ofbronchodilators or local steroid injections would not be excluded from the study.Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement orpsoriasis not requiring treatment are not excluded from the study.
• Live vaccine within 30 days prior to the first dose of Tislelizumab treatment orduring study treatment.
• History or clinical evidence of Central Nervous System (CNS) metastases Exceptionsare: Subjects who have completed local therapy and who meet both of the followingcriteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks priorto start of Tislelizumab treatment. Screening with CNS imaging (CT or MRI) is requiredonly if clinically indicated or if the subject has a history of CNS
• Medication that is known to interfere with any of the agents applied in the trial.
• Any other efficacious cancer treatment except protocol specified treatment at studystart.
• Patient has received any other investigational product within 28 days of study entry.
• Female subjects who are pregnant, breast-feeding or male/female patients ofreproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are:implants, injectable contraceptives, combined oral contraceptives, intrauterinepessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Womenof childbearing potential must have a negative pregnancy test (serum β-HCG) atscreening. Patient with any significant history of non-compliance to medical regimens or withinability to grant reliable informed consent.