study of a c-met inhibitor plb1001 in patients with ptprz1-met fusion gene positive recurrent high-grade gliomas

Conditions: Glioma

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.

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.

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