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

NCT02412462 | Completed Phase 1

• 1 other identifier: AB-16B5-101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor; Metastatic Cancer

Keywords

Phase I; Clusterin; Epithelial-to-Mesenchymal Transition (EMT); Circulating Tumor Cells (CTC); EMT and Stem Cell Biomarkers; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

AB-16B5

EXPERIMENTAL

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

Interventions

AB-16B5 DRUG

AB-16B5

Eligibility Criteria

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

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alethia Biotherapeutics: lead

Study Sites (1)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplastic Cells, Circulating

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 9, 2015
• Study Start: April 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: June 28, 2017

Record last verified: 2016-07

Locations

CA (1)