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

NCT ID: NCT02978261

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-12-31

Brief 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.

Detailed 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.

Conditions

Glioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PLB1001

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.

Group Type: EXPERIMENTAL

PLB1001

Intervention Type: DRUG

PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.

Interventions

PLB1001

PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.

Intervention Type: DRUG

Other Intervention Names

Bozitinib

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Pearl Biotechnology Limited Liability Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenbin Li, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Shijitan Hospital, CMU

Locations

Beijing Shijitan Hospital,CMU

Beijing, Beijing Municipality, China

Countries

China

References

Hu H, Mu Q, Bao Z, Chen Y, Liu Y, Chen J, Wang K, Wang Z, Nam Y, Jiang B, Sa JK, Cho HJ, Her NG, Zhang C, Zhao Z, Zhang Y, Zeng F, Wu F, Kang X, Liu Y, Qian Z, Wang Z, Huang R, Wang Q, Zhang W, Qiu X, Li W, Nam DH, Fan X, Wang J, Jiang T. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell. 2018 Nov 29;175(6):1665-1678.e18. doi: 10.1016/j.cell.2018.09.038. Epub 2018 Oct 18.

Reference Type: DERIVED

PMID: 30343896 (View on PubMed)

Other Identifiers

HMO-PLB1001-I-GBM-01

Identifier Type: -

Identifier Source: org_study_id