Phase I Dose Escalation Study of AB-16B5 in Subjects With an Advanced Solid Malignancy

A Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AB-16B5 in Subjects With an Advanced Solid Malignancy

This is a Phase 1 clinical study to investigate the safety, pharmacokinetics and pharmacodynamics of AB-16B5 in patients with an advanced solid malignancy. AB-16B5 is a humanized monoclonal antibody that inhibits the activity of the secreted form of clusterin (sCLU), a potent inducer of the epithelial-to-mesenchymal transition (EMT). Eligible subjects will have a disease that has been refractory to prior therapy and is unlikely to benefit from known therapies.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Metastatic Cancer
• Intervention / Treatment: Drug: AB-16B5

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a histologically or cytologically confirmed advanced solid malignancy that has been refractory to prior therapy and is unlikely to benefit from known therapies.
• Subjects may have measurable or non-measurable but evaluable disease.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 and an estimated life expectancy of at least 12 weeks.
• Subjects must be ≥ 18 years old.
• Male, or female subjects who are post-menopausal (amenorrheic for at least 12 months), or surgically or biologically sterile. Females of childbearing potential with a negative serum pregnancy test prior to entering the study and using adequate forms of contraception for the duration of the study, including 30 days after the last treatment. Males should avoid fathering children during the course of the study, and adequate methods of contraception should be used by both male and female subjects. Subjects and their partners with reproductive potential must use an effective contraceptive method while the subject is on the study treatment and for 30 days after the last treatment.

• Subjects must have adequate organ and immune function as indicated by the following laboratory values:

  • ANC ≥ 1.5 X 109/L
  • Platelets > 100 X 109/L
  • Hemoglobin ≥ 90 g/L
  • Serum creatinine ≤ 132 µmol/L
  • Total Bilirubin ≤ 1.5 X ULN

  • AST (SGOT) and ALT (SGPT) ≤ 3 X ULN* or;

    • 5 X ULN* (if hepatic metastases present)

      • ULN: Institution's upper limit of normal
• Subjects enrolled in the standard dose escalation portion of the study must have a tumor lesion amenable for biopsy with no contraindications for biopsy.
• Subjects must understand and be able and willing and likely to fully comply with the study procedures, including scheduled follow-up, and restrictions.
• Subjects must have given written personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, before completing any study related procedures.

Exclusion Criteria:

• Subjects with medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures.
• Prior cancer therapy including surgery, radiotherapy, chemotherapy, hormonal and biological therapies within 3 weeks prior to study treatment.
• Uncontrolled brain metastases.
• Uncontrolled infection.
• Clinically significant ECG abnormalities.
• Known hypersensitivity of Grade > 2 to previous monoclonal antibody therapy.
• History of alcohol or other substance abuse within the last year.
• Use of another investigational agent in a clinical trial within the last 4 weeks prior to study treatment.
• Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening must be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AB-16B5; Single-arm study of AB-16B5 given as a 60-minute intravenous weekly infusion. One cycle of treatment will consist of 21 days. The dose levels that will be assessed are 1.5, 3.0, 6.0, 9.0 and 12 mg/kg.	Drug: AB-16B5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with an adverse event as a measure of safety and tolerability	Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Determination of plasma concentrations of AB-16B5	Several time-points during Cycle 1 and Cycle 2 for a total of 6 weeks
Objective tumor responses in subjects with measurable disease according to RECIST	Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks
Monitoring of epithelial-to-mesenchymal (EMT) and stem cells biomarkers in peripheral blood circulating tumor cells and paired tumor biopsies	Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks

Collaborators and Investigators

• Sponsor: Alethia Biotherapeutics

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: April 6, 2015
• First Posted (Estimate): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase I; Clusterin; Epithelial-to-Mesenchymal Transition (EMT); Circulating Tumor Cells (CTC); EMT and Stem Cell Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: AB-16B5-101