A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).

Beijing Pearl Biotechnology

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Glioblastoma

Treatments: Drug: Temozolomide; Drug: Cisplatin combined with Etoposide; Drug: PLB1001

Study type: Interventional

Funder types: Industry

Identifiers

NCT06105619

PLB1001-Ⅱ-GBM-01

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the safety and efficacy of PLB1001 Enteric Capsules in the treatment of PTPRZ1-MET fusion gene positive recurrent secondary glioblastoma. The main questions it aims to answer are:

1. To evaluate overall survival (OS) in the treatment of secondary glioblasts with positive recurrence of PTPRZ1-MET (ZM) fusion gene by PLB1001 Enteric Capsules.
2. To evaluate if it is safety and tolerant in the treatment of secondary glioblasts with positive recurrence of PTPRZ1-MET (ZM) fusion gene by PLB1001 Enteric Capsules.

Participants will

1. Be given PLB1001 300mg BID,oral who were randomly assigned in test group.
2. Be given Temozolomide capsules ,oral, who were randomly assigned in control group.
3. Be given EP, ivgtt, who were randomly assigned in control group.

Full description

84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene will be randomly divided into group A (receive vebreltinib) or group B ( receive investigator choose), and the randomize ratio will be 1:1, patients in group A will receive PLB1001 300mg Bid, 28days/cycle. Patients in group B will receive temozolomide (100-150mg/m2/d, 7 days 1 to7 and days 15 to 22 of each 28-day cycle ) or cisplatin+etoposide(cisplatin:80-100mg/m2/3 days, 28days/cycle; etoposide:100mg/m2/d, 3days, 28 days/cycle).

Enrollment: 84 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. histologically confirmed secondary glioblastoma,or glioblastoma with IDH mutantation
2. Must have evidence of PRPRZ1-MET fusion gene positivity from the result of molecular pre-screening evaluations
3. Prior treatment with temozolomide and radiotherapy
4. Stable or decreasing dose of corticosteroids within 5 days prior to the first dose
5. Platelet count≥75×109/L,Neutrophilic granulocyte count≥1.5×109/L, Hemoglobin>90g/L,AST or ALT < 3 times the lab's upper normal limit,Serum creatinine < 1.5 times the lab's upper normal limit,INR≤2.0
6. Karnofsky performance score ≥ 60%
7. Pregnant or nursing women
8. Written consent

Exclusion criteria

1. Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy
2. Received antibody anti-tumor drug within 30 days before enrollment
3. Previous treatment with Camustine sustained release implant
4. The subject is unable to undergo MRI scan
5. Patients with active bleeding were found by brain CT or MRI scan before enrollment
6. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) 150 mm Hg and/or Diastolic Blood Pressure (DBP) ≥100 mm Hg
7. Major surgery within 4 weeks prior to first dose of PLB1001
8. Pregnant or nursing women
9. Involved in other clinical trials <30 days prior to first dose

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 2 patient groups

PLB1001

Experimental group

Description:

Subjects will receive 300mg of PLB1001 twice daily in cycles of 4 weeks duration until death or adverse event(AE) leading to discontinuation

Treatment:

Drug: PLB1001

Temozolomide or Cisplatin combined with etoposide

Active Comparator group

Description:

Investigators can choose one of two treatments 1. Dose density of temozolomide：100-150mg/m2/d,day 1 to 7 and day 15 to 22 of each 28-day cycle 2. Cisplatin combined with etoposide：Cisplatin,80-100mg/m2/3 days,28 days/cycle.etoposide, 100mg/m2/d,3 days,28 days/cycle

Treatment:

Drug: Cisplatin combined with Etoposide

Drug: Temozolomide