Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions

NCT03869697 | Completed Phase 1

• 1 other identifier: CLO-SCB-313-002
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Malignant Pleural Effusions

Outcome Measures

Primary Outcomes (1)

• Occurrence of DLT

  Occurrence of dose limiting toxicity (DLT)

  Up to 21 days after start of treatment

Secondary Outcomes (33)

• SAEs or TEAEs

  Up to 21 days after start of treatment

• Immunogenicity

  Up to 21 days after start of treatment

• Pleural effusion response rate at Day 21

  At Day 21 after start of treatment

• Pleural effusion drainage-free rate at Day 21

  At Day 21 after start of treatment

• The changes in effusion volume and flow rate after SCB-313 treatment , and at next drainage over the baseline daily effusion flow rate.

  Up to 6 months after start of treatment

Study Arms (1)

SCB-313

EXPERIMENTAL

Cohorts in SAD phase: 5 mg, 10mg, 20mg, 40mg, 80 mg. Cohort in MAD phase: biological effective dose determined from SAD phase. 1 intrapleural injection of SCB-313 on Day 1 for the SAD cohorts, and 3 intrapleural injections of SCB-313 on Days 1, 2 and 3 for the MAD cohort.

Drug: SCB-313

Interventions

SCB-313 DRUG

5 mg or 20 mg lyophilized powder in a single-use glass 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 cancer of any primary tumor type.
• 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.
• 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.
• Life expectancy of at least 8 weeks.
• Age ≥18 years.
• Adequate hematologic 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 creatinine clearance \>40 mL/minute.
• Adequate liver function, defined as:
• Aspartate aminotransferase and alanine aminotransferase ≤2.0 times ULN;
• Bilirubin ≤2.0 times ULN, unless patient has known Gilbert's syndrome.
• 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.

You may not qualify if:

• Significantly loculated pleural effusions not amenable to drainage or patient is unlikely to benefit from intrapleural therapy.
• Concurrent use of any investigational product (IP) or investigational medicine within 28 days before Day 1 of study drug administration.
• 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).
• 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.
• Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
• Clinical unstable or uncontrolled concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
• History of gross hemoptysis (\>2.5 mL).
• 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 \>480 msec at Baseline.
• 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).
• Major surgery (open procedures) 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/or 2, or known history of other immunodeficiency disease.
• Live vaccine within 2 weeks prior to enrollment.

Sponsors & Collaborators

• Clover Biopharmaceuticals AUS Pty: lead

Study Sites (4)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Orange Health Service

Orange, New South Wales, 2800, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

SCGH (Sir Charles Gairdner Hospital)

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Pleural Effusion, Malignant

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases

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: March 1, 2019
• First Posted: March 11, 2019
• Study Start: November 20, 2019
• Primary Completion: November 4, 2021
• Study Completion: November 23, 2021
• Last Updated: February 2, 2022

Record last verified: 2022-02

Locations

AU (4)