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

NCT03443674 | Completed Phase 1

• 1 other identifier: CLO-SCB-313-001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Peritoneal Malignancies

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Occurrence of serious adverse events (SAEs) and/or TEAEs

  Regardless of causality or relationship to SCB-313 graded using National Cancer Institute Common Terminology Criteria for Adverse Events Version.4.03 (NCI CTCAE v4.03).

  Up to 41 days after start of treatment

Secondary Outcomes (8)

• Immunogenicity: Occurrence of binding and neutralizing anti-SCB-313 antibodies

  Up to 41 days after start of treatment

• Pharmacokinetics (Cmax)

  Up to 12 days after start of treatment

• Pharmacokinetics (Cmax/D)

  Up to 12 days after start of treatment

• Pharmacokinetics (tmax)

  Up to 12 days after start of treatment

• Pharmacokinetics ([AUC]0-24)

  Up to 12 days after start of treatment

Other Outcomes (2)

• CEA

  Up to 6 months after start of treatment

• Caspase-cleaved cytokeratin 18 (CK-18)

  Up to 21 days after start of treatment

Study Arms (1)

SCB-313

EXPERIMENTAL

Dose escalation cohorts--10mg, 20mg, 40mg, 80mg, 160mg. For each cohort: administered twice weekly (eg.. Monday and Thursday or Tuesday and Friday) for 2 weeks (Days 1, 4, 8, and 11) by IP bolus injection.

Drug: SCB-313

Interventions

SCB-313 DRUG

Lyophilized powder in a single-use vial

Also known as: recombinant human TRAIL-Trimer fusion protein

SCB-313

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed peritoneal malignancies after failure or refusal of all approved therapies, and no better option available in the Investigator's opinion.
• 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)
• Life expectancy of at least 8 weeks
• Age ≥18 years
• Body mass index ≥17.0 kg/m2
• Adequate hematological function, defined as:
• Platelet count ≥ 75,000/μL
• Prothrombin time and activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN)
• Absolute neutrophil count ≥1,500/μL
• 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)
• Adequate renal function, defined as serum creatinine ≤2.0 times ULN and creatinine clearance \>45 mL/minute
• Adequate liver function, defined as:
• Aspartate aminotransferase and alanine aminotransferase ≤3 times ULN for patients without liver metastases, or ≤5 times ULN in the presence of liver metastases
• Bilirubin ≤1.5 times ULN, unless patient has known Gilbert's syndrome
• 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.

You may not qualify if:

• Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous (IV) antibiotics within 2 weeks prior to enrollment.
• Symptoms or signs (including laboratory tests) of clinically significant concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
• Residual adverse events (AEs) \> Grade 2 from previous treatment.
• Evidence or suspicion of relevant psychiatric impairment including alcohol or recreational drug abuse.
• 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.
• Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures.
• Left ventricular ejection fraction \<40% as determined by echocardiography performed at screening or within 90 days prior to enrollment.
• 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.
• Major surgery within 4 weeks prior to enrollment.
• Patient with ileus within 30 days prior to screening.
• Positive serology test for human immunodeficiency virus Type 1 and 2 or known history of other immunodeficiency disease.
• Live vaccine within 2 weeks prior to enrollment.
• Scheduled participation in another clinical study involving an investigational product or device during the course of this study.
• Previous treatment with a TRAIL-based therapy or death receptor (DR) 4/5 agonist therapy.
• Known or suspected hypersensitivity to any component of the SCB-313.

Sponsors & Collaborators

• Clover Biopharmaceuticals AUS Pty: lead

Study Sites (5)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Orange Health Service

Orange, New South Wales, 2800, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

John Flynn Private Hospital

Tugun, Queensland, 4224, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2018
• First Posted: February 23, 2018
• Study Start: June 18, 2018
• Primary Completion: May 30, 2021
• Study Completion: August 26, 2021
• Last Updated: October 19, 2021

Record last verified: 2021-10

Locations

AU (5)