Overview

This is a Phase I/II, open, first-in-human (FIH) study of Transebacillus in Patients with malignant pleural and abdominal effusions. It consists of Phase Ia to determine the Maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D) of Transebacillus, and Phase Ib/II to explore and confirm the efficacy, safety and Tolerability.

Eligibility

Inclusion Criteria:

• Voluntarily participate, sign the informed consent, and good compliance, able to cooperate with the diagnosis and treatment and follow-up;
• Age ≥18 years old (inclusive), male and female are not limited;
• Malignant solid tumors other than primary hepatocellular carcinoma confirmed by pathological histological or cytological examination;
• Malignant thoracic/abdominal effusion patients who have failed at least one standard antitumor systemic therapy, are not suitable for standard systemic therapy, or have no standard systemic therapy. The pleural/abdominal effusion needs to be confirmed pathologically (malignant cells found in the cytosol or pathological changes of malignancy observed in the pleural/peritoneal biopsy tissue) or clinically diagnosed as malignant pleural/abdominal effusion;
• A pleural/peritoneal effusion of intermediate or greater volume confirmed by ultrasound, which in clinical judgment requires localized treatment of the pleural/ peritoneal effusion; definition of intermediate or greater volume: maximum depth of pleural effusion ≥ 3 cm by ultrasound in sitting position; or maximum depth of abdominal effusion ≥ 4 cm by ultrasound in lying position;
• KPS score ≥ 60;
• Expected survival ≥ 3 months;
• Major organ function is essentially normal and laboratory tests；
• Screening female subjects of childbearing potential with a negative serum pregnancy test; female/male subjects of childbearing potential must be willing to use a reliable method of contraception throughout the study period (i.e., from the time of signed informed consent to 90 days after the last dose of study medication), including, but not limited to, abstinence, a male partner who has undergone a vasectomy, female sterilization, an effective intrauterine device, and effective contraceptives.
• Patients are willing to participate in the study, sign an informed consent form, and have good compliance.

Exclusion Criteria:

• Participating in or has participated in another clinical trial with investigational therapy within 4 weeks prior to first dose, or has participated in a device clinical trial within 4 weeks;
• has received systemic antitumor therapy or a drug in the thoracic-abdominal cavity within 14 days of the first intratumoral administration;
• less than 4 weeks since the need for re-puncture/drainage due to progression of the effusion after having received intraluminal therapy with cisplatin and/or an anti-angiogenic drug (e.g., Endo, bevacizumab, etc.) for the thoracic-abdominal effusion that is the subject of the treatment planned for this study;
• Has not recovered from any intervention-induced adverse event ≤ Grade 1 (except for hair loss, hearing impairment, and neurologic or endocrine disorders ≤ Grade 2 requiring replacement therapy) prior to the first dose;
• Subjects who have undergone a medium to major surgical procedure other than diagnostic or biopsy within 28 days prior to the first dose, or who are expected to undergo a major surgical procedure during the study period;
• Bilateral pleural effusion (for patients with pleural effusion) or concomitant thoracoabdominal effusion (non-enrolled treatment cavities that have not reached a moderate volume of effusion and, in the judgment of the investigator, are in stable condition and do not require clinical management may be considered for enrollment), or pericardial effusion (more than a moderate volume or with associated symptoms that, in the judgment of the investigator, require treatment) or an encapsulated effusion or celiac disease on the side of the planned treatment or have undergone within 14 days prior to the first administration of the study medication Therapeutic puncture and/or drainage (presence of suspected symptoms of effusion as well as previous history of effusion, B-ultrasound is required during the Screening Period to confirm the amount of effusion in the non-enrolled treatment cavity);
• Comorbid severe chronic obstructive pulmonary disease (global initiative for chronic obstructive lung disease (GOLD) ≥ 3), intestinal adhesions within 6 months prior to the first dose (except in patients with pleural effusions in the treatment cavity) or intestinal obstruction within 6 months prior to the first dose. Bowel obstruction within 6 months prior to the first dose;
• Severe cardiovascular disease such as New York Heart Association (NYHA) heart disease (Class III rating or better) or myocardial infarction within 6 months or current unstable angina pectoris or uncontrolled hypertension (systolic blood pressure greater than 150 mmHg and/or diastolic blood pressure greater than 100 mmHg);
• Patients with uncontrolled primary brain tumors or CNS metastases with significant intracranial hypertension or neuropsychiatric symptoms;
• Presence of uncontrolled neuropsychiatric disease, psychiatric disorders, or substance abuse that may affect compliance with the trial;
• The presence of an uncontrollable neuropsychiatric disease, psychiatric disorder, or substance abuse that may interfere with trial compliance;
• Presence of an active infection requiring systemic therapy;
• A known history of human immunodeficiency virus (HIV) infection;
• Hepatitis B virus-infected patients (HBsAg-positive or HBcAb-positive with HBV-DNA ≥2000 IU/mL or HBV-DNA ≥104 copies/mL), or Hepatitis C virus-infected patients (HCV antibody-positive with HCV-RNA quantitative test results greater than the lower limit of detection); Note: For HBV-DNA <2000 IU/mL Note: Hepatitis B virus-infected patients with HBV-DNA <2000 IU/mL or HBV DNA <104 copies/mL may be enrolled if they are willing to be treated with entecavir, tenofovir, or other antiviral therapy during the study period based on clinical judgment;
• Individuals who are allergic to any active or inactive ingredient of entrectal or co-administered chemotherapeutic agents;
• Pregnant or lactating female patients;
• Use of antibiotic drugs with caution;
• Presence of medical history or disease, therapeutic or laboratory abnormality that has the potential to interfere with the results of the trial, to prevent the subject from participating in the study in its entirety, or where participation in the study is not, in the opinion of the investigator, in the best interest of the subject.