Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Peritoneal Malignancies

A Phase I Study Evaluating Safety, Tolerability, and Pharmacokinetics of SCB-313, a Fully-Human TRAIL-Trimer Fusion Protein, for the Treatment of Peritoneal Malignancies

The purpose of this study is to evaluate the safety, tolerability, immunogenicity, and PK/PD of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered twice weekly for 2 weeks via IP bolus injection for the treatment of patients with peritoneal malignancies, including but not limited to peritoneal carcinomatosis, malignant ascites, pseudomyxoma peritonei, and peritoneal mesothelioma.

Inclusion Criteria:

1. Histologically or cytologically confirmed peritoneal malignancies after failure or refusal of all approved therapies, and no better option available in the Investigator's opinion.

2. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2 (Patients with ECOG score of 3 might be allowed to enter this trial per Investigator's judgment)

3. Life expectancy of at least 8 weeks

4. Age ≥18 years

5. Body mass index ≥17.0 kg/m2

6. Adequate hematological 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 serum creatinine ≤2.0 times ULN and creatinine clearance >45 mL/minute

8. Adequate liver function, defined as:

   1. Aspartate aminotransferase and alanine aminotransferase ≤3 times ULN for patients without liver metastases, or ≤5 times ULN in the presence of liver metastases
   2. Bilirubin ≤1.5 times ULN, unless patient has known Gilbert's syndrome

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

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

Exclusion Criteria:

1. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous (IV) antibiotics within 2 weeks prior to enrollment.
2. Symptoms or signs (including laboratory tests) of clinically significant concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
3. Residual adverse events (AEs) > Grade 2 from previous treatment.
4. Evidence or suspicion of relevant psychiatric impairment including alcohol or recreational drug abuse.
5. 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 >450 msec at baseline.
6. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures.
7. Left ventricular ejection fraction <40% as determined by echocardiography performed at screening or within 90 days prior to enrollment.
8. Prior anti-tumor therapy (chemotherapy) within 2 weeks, hormone therapy or palliative extra-abdominal radiotherapy within at least 1 week, or small-molecule targeted therapy within 5 half-lives prior to enrollment. Prior therapy with monoclonal antibody should be stopped after Investigator's judgement making sure delayed side effects will not interfere with the dose limiting toxicity (DLT) evaluation period after SCB-313 therapy.
9. Major surgery within 4 weeks prior to enrollment.
10. Patient with ileus within 30 days prior to screening.
11. Positive serology test for human immunodeficiency virus Type 1 and 2 or known history of other immunodeficiency disease.
12. Live vaccine within 2 weeks prior to enrollment.
13. Scheduled participation in another clinical study involving an investigational product or device during the course of this study.
14. Previous treatment with a TRAIL-based therapy or death receptor (DR) 4/5 agonist therapy.
15. Known or suspected hypersensitivity to any component of the SCB-313.
16. Any further condition which, according to the Investigator, may result in undue risk of the patient by participating in the present study.
17. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.