First-in-Human Expanded Cohort Study of Intrapleural Administration of TolueneSulfonamide in Patients With Malignant Pleural Effusion

This study is a first-in-human (FIM) expansion cohort study designed to evaluate the safety and clinical activity of intrapleural injection of PTS in patients with malignant pleural effusion (MPE). Patients with MPE will be prospectively enrolled, and the study will be conducted in two parts: a safety and dose-exploration phase of intrapleural PTS administration (Part 1, P1), followed by an efficacy evaluation phase of intrapleural PTS for the treatment of MPE (Part 2, P2). Part 2 will be initiated after the safety of PTS has been established in Part 1.

Part 1 is designed as a prospective, single-arm, open-label study. Part 2 is designed as a prospective, multicenter, double-blind, randomized controlled trial with two groups: an experimental group and a control group. The experimental group will receive catheter drainage plus intrapleural PTS injection, while the control group will receive catheter drainage plus intrapleural normal saline injection.

Inclusion criteria

• Age between 18 and 75 years (inclusive) at the time of signing the informed consent form.
• Histologically or cytologically confirmed malignant pleural effusion, with the primary tumor diagnosed as non-small cell lung cancer (NSCLC).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of at least 3 months.
• Presence of dyspnea symptoms.
• No prior local thoracic treatment within 1 month before enrollment, including intrapleural drug administration or thoracic radiotherapy (diagnostic thoracentesis is permitted).
• Except for the subject's current stable systemic anti-tumor therapy, any other ongoing tumor-related treatments must be suspended or discontinued after evaluation by the investigator to ensure they do not interfere with the assessment of PTS treatment.
• Fully understands the study objectives and procedures, agrees to participate in the study, and provides written informed consent.

Exclusion criteria

• History of allergy or hypersensitivity to PTS or any of its excipients.
• Presence of uncontrolled intrapleural infection or severe loculated pleural effusion that is difficult to manage.
• Participation in another interventional clinical study within 3 months prior to enrollment (diagnostic studies are excluded).
• Severe organ dysfunction, including but not limited to coagulation disorders, congestive heart failure, malignant arrhythmias, coronary artery disease requiring long-term medication, valvular heart disease, myocardial infarction, or refractory hypertension; severe cardiac, hepatic, or renal insufficiency, or active bleeding or thrombotic risk.
• Presence of uncontrolled infectious wounds.
• Pregnant or breastfeeding women.
• Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.
• Criteria for withdrawal from the study.