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

Clover Biopharmaceuticals AUS Pty Ltd4 sites in 1 country5 target enrollmentNovember 20, 2019

ConditionsMalignant Pleural Effusions

InterventionsSCB-313

DrugsSCB-313

Overview

Phase: Phase 1
Intervention: SCB-313
Conditions: Malignant Pleural Effusions
Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
Enrollment: 5
Locations: 4
Primary Endpoint: Occurrence of DLT
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 20, 2019

End Date

November 23, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Clover Biopharmaceuticals AUS Pty Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•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;

Exclusion Criteria

•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.

Arms & Interventions

SCB-313

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.

Intervention: SCB-313

Outcomes

Primary Outcomes

Occurrence of DLT

Time Frame: Up to 21 days after start of treatment

Occurrence of dose limiting toxicity (DLT)

Secondary Outcomes

Carcinoembryonic antigen (CEA)(Up to 21 days after start of treatment)
Pleural effusion drainage-free rate at Day 21(At Day 21 after start of treatment)
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)
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)
Blood oxygen levels(Up to 21 days after start of treatment)
Overall survival(Up to 6 months after start of treatment)
Pharmacokinetics (Cmax)(Up to 4 days after start of treatment)
Pharmacokinetics(Cmax/D)(Up to 4 days after start of treatment)
Pharmacokinetics(Tmax)(Up to 4 days after start of treatment)
Pharmacokinetics ([AUC]0-24)(Up to 4 days after start of treatment)
Pharmacokinetics (AUC0-24/D)(Up to 4 days after start of treatment)
Pharmacokinetics ((AUC0-last))(Up to 4 days after start of treatment)
Pharmacokinetics (Ctrough)(Up to 4 days after start of treatment)
Amount of drug in pleural effusion(Up to 4 days after start of treatment)
Pharmacokinetics (AUC 0-inf)(Up to 4 days after start of treatment)
Pharmacokinetics (AUC0-inf/D)(Up to 4 days after start of treatment)
Pharmacokinetics (t1/2)(Up to 4 days after start of treatment)
Pharmacokinetics (CL/F serum only)(Up to 4 days after start of treatment)
Pharmacokinetics (Vz/F serum only)(Up to 4 days after start of treatment)
Pharmacokinetics (λz)(Up to 4 days after start of treatment)
Tumor response(Up to 6 months after start of treatment)
TRAIL resistance(Baseline)
CA-125(Up to 21 days after start of treatment)
CA-19-9(Up to 21 days after start of treatment)
Changes in 24-hour urine volume(Up to 4 days after start of treatment)
Changes in GFR(Up to 4 days after start of treatment)
Changes in tumor cell count in pleural effusion samples(Up to 4 days after start of treatment)
Caspase-cleaved CK18(Up to 10 days after start of treatment)
KRAS mutation(Baseline)
MMR defects(Baseline)
Bcl2 overexpression(Baseline)