The purpose of this study is to evaluate the safety, tolerability, preliminary efficacy, and PK/PD of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered once via intrapleural injection (SAD) and once daily over 2 to 3 days (MAD)for the treatment of cancer patients with symptomatic malignant pleural effusions requiring drainage.

Inclusion Criteria:

1. Histologically or cytologically confirmed cancer of any primary tumor type.

2. Malignant pleural effusion causing respiratory symptoms requiring drainage that is histologically or cytologically confirmed; or pleural effusion with radiologically proven pleural malignancy as diagnosed in normal clinical practice on thoracic computed tomography in the absence of histocytological or cytological proof.

3. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2. Patients with an ECOG performance status of 3 may be included if the Investigator determines that removal of pleural fluid would improve their performance status to 2 or better.

4. Life expectancy of at least 8 weeks.

5. Age ≥18 years.

6. Adequate hematologic function, defined as:

   1. Platelet count ≥75,000/μL;
   2. Prothrombin time and activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN);
   3. Absolute neutrophil count ≥1,500 μL;
   4. Hemoglobin ≥8 g/dL (transfusion and erythropoietic agents are allowed). In case there is existence of active bleeding or other persistent condition of either increased destruction or impaired production of erythrocytes, which may require repeated transfusion or erythropoietic treatment, the eligibility must be discussed with the Sponsor on a case-by-case basis prior to randomization).

7. Adequate renal function, defined as creatinine clearance >40 mL/minute.

8. Adequate liver function, defined as:

   1. Aspartate aminotransferase and alanine aminotransferase ≤2.0 times ULN;
   2. Bilirubin ≤2.0 times ULN, unless patient has known Gilbert's syndrome.

9. Female patients of childbearing potential (excluding women who have undergone surgical sterilization or are menopausal, defined as no menstrual periods for 1 year or more without any other medical reasons) are eligible if they have negative serum pregnancy test result 7 days before the first dose of SCB-313 and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after discontinuation of SCB-313.

   Both men and women of reproductive potential must agree to use effective contraception during the study and for 6 months after discontinuation of SCB-313.

   Note: Contraceptive methods that are considered highly effective areas follows: total abstinence, intrauterine device, double barrier method (such as condom plus diaphragm with spermicide), contraceptive implant, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release), or vasectomized partner with confirmed azoospermia.

10. Willing to attend follow-up visits on Days 10, and 21 after the first study drug administration.

Exclusion Criteria:

1. Significantly loculated pleural effusions not amenable to drainage or patient is unlikely to benefit from intrapleural therapy.
2. Concurrent use of any investigational product (IP) or investigational medicine within 28 days before Day 1 of study drug administration.
3. Radiotherapy outside the chest field within 2 weeks, or radical radiotherapy to pleural or lung lesions within 8 weeks prior to enrollment (Note: palliative radiotherapy to the chest is allowed).
4. Start a new systemic anticancer therapy, including chemotherapy, targeted therapy, immuno-oncology (I-O) therapy regimen, within 28 days before Day 1 of study drug administration or during DLT observation period.
5. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
6. Clinical unstable or uncontrolled concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
7. History of gross hemoptysis (>2.5 mL).
8. Residual adverse events (AEs) > Grade 2 from previous treatment.
9. Evidence or suspicion of relevant psychiatric impairment, including alcohol or recreational drug abuse.
10. Myocardial infarction within 6 months prior to treatment and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication, and/or long QT syndrome or QT/QTc interval >480 msec at Baseline.
11. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures (note: no more than 3 repeated measures allowed).
12. Major surgery (open procedures) within 4 weeks prior to enrollment.
13. Patient with ileus within 30 days prior to Screening.
14. Positive serology test for human immunodeficiency virus type 1 and/or 2, or known history of other immunodeficiency disease.
15. Live vaccine within 2 weeks prior to enrollment.
16. Scheduled participation in another clinical study involving an investigational product or device during the DLT observation period of this study.
17. Previous treatment with a TRAIL-based therapy or death receptor 4/5 agonist therapy.
18. Known or suspected hypersensitivity to any component of SCB-313.
19. Any further condition which, in the opinion of the Investigator, may result in undue risk of the patient by participating in the present study.
20. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.