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

Beijing Pearl Biotechnology

Status and phase: Completed; Phase 1

Conditions: Glioma

Treatments: Drug: PLB1001

Study type: Interventional

Funder types: Industry

Identifiers

NCT02978261

HMO-PLB1001-I-GBM-01

Details and patient eligibility

About

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.

Full description

This is a Phase I, open-label study of PLB1001 administered orally to patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas. The aim of dose-escalation study is to estimate the MTD and to identify the dose-limiting toxicity(DLT) and the recommended phase II dose (RP2D) for PLB1001 single agent as well as to determine the PK/PD profile. Aprox. 20 patients will be enrolled in this study.

PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal cMET-mediated signaling (including PTPRZ1-MET fusion gene), leading to profound tumor growth inhibition in xenografts of PTPRZ1-MET fusion gene positive glioblastoma tumor.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

PLB1001

Experimental group

Description:

There are 4 dose cohorts, including 50mg BID,100mg BID, 200mg BID and 300mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.

Treatment:

Drug: PLB1001