Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas

• Status: Completed
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I, open-label, dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of single and multiple doses of PLB1001 in Patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beijing Pearl Biotechnology Limited Liability Company

Criteria

Inclusion Criteria:

• Signed Informed Consent Form

• Age≥18 years

• Histologically or cytologically confirmed recurrent high-grade glioma after concurrent or adjuvant chemoradiotherapy

• Prior treatment with temozolomide

• Must have evidence of PTPRZ1-MET fusion gene positivity from the results of molecular pre-screening evaluations

• At least one measurable lesion as per RANO

• No evidence of recent haemorrhage on baseline MRI of the brain

• Stable or decreasing dose of corticosteroids within 5 days prior to the first dose

• Major surgery within 4 weeks prior to first dose of PLB1001

• Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001

• Pregnant or nursing women

• Involved in other clinical trials <30 days prior to first dose

• Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field

• Karnofsky performance status ≥ 50%

Exclusion Criteria:

• Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy

• The subject is unable to undergo MRI scan (e.g. has pacemaker)

• Clinically significant, uncontrolled heart diseases： Unstable angina; History of documented congestive heart failure (New York Heart Association functional classification> II); Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 145 mm Hg and/or Diastolic Blood Pressure (DBP) ≥85 mm Hg; Arrhythmias.

• Active peptic ulcer disease or gastritis

• Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1, except for alopecia

• Major surgery within 4 weeks prior to first dose of PLB1001

• Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001

• Pregnant or nursing women

• Involved in other clinical trials <30 days prior to first dose