Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI

Phase 1

Recruiting

• Conditions: Non-Small-Cell Lung Cancer
• Interventions: Drug: Vebreltinib; Drug: PLB1004

• Registration Number: NCT06343064
• Lead Sponsor: Avistone Biotechnology Co., Ltd.

Brief Summary

Efficacy and Safety Evaluation of Vebreltinib Plus PLB1004 in EGFR TKI Relapsed MET Amplified or MET Expression in NSCLC

Detailed Description

Open label, multicenter Phase Ib/II clinical study to evaluate the safety, efficacy, and pharmacokinetics of Vebreltinib in combination with PLB1004 in patients with locally advanced or metastatic non-small cell lung cancer with MET overexpression or MET amplification following EGFR-TKI treatment failure.

Study Timeline

• Study Start: 2023-06-13
• Study First Submitted: 2024-03-21
• Study First Submitted QC: 2024-03-26
• Study First Posted: 2024-04-02
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 156

Inclusion Criteria

1. Ability to understand and willingness to sign a written informed consent document.
2. Aged at least 18 years old.
3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
4. EGFR mutations, including exon 19 deletion and exon 21 L858R.
5. C-Met overexpression and/or c-Met amplification confirmed after treatment with EGFR-TKI.
6. At least one measurable lesion as defined by RECIST V1.1.
7. ECOG performance status 0 to 1.

Exclusion Criteria

1. Previous treatment with MET inhibitors or HGF-targeted therapy.
2. There are mutations of ALK or ROS1.
3. Have symptomatic and neurologically unstable central nervous system (CNS) metastases or CNS disease that requires increased steroid doses for control.
4. Pregnant or nursing women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD	PLB1004	In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.
Phase II:Cohort 2	Vebreltinib	In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD	Vebreltinib	In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.
Phase II:Cohort 1	Vebreltinib	In phase II-Cohort 1:Failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Phase II:Cohort 2	PLB1004	In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Phase II:Cohort 3	PLB1004	In phase II-Cohort 3 :Failed first-generation or second-generation EGFR inhibitors, c-Met over expression.Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Phase II:Cohort 1	PLB1004	In phase II-Cohort 1:Failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Phase II:Cohort 3	Vebreltinib	In phase II-Cohort 3 :Failed first-generation or second-generation EGFR inhibitors, c-Met over expression.Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities (DLT) as defined in the protocol.	28 days	In phase Ib，Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).	3 years	In phase Ib，Incidence of Treatment-Emergent Adverse Events (TEAEs),
Overall Response Rate (ORR）	3 years	In phase II,ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of Vebreltinib and PLB1004: Maximum plasma concentration of the study drug (C-max)	From date of first dose up until 28 days post last dose	In phase Ib，Measurement of PK parameters: Maximum observed plasma concentration of the study drug (C-max)
Pharmacokinetics of Vebreltinib and PLB1004: Time to maximum plasma concentration of the study drug (T-max)	From date of first dose up until 28 days post last dose	In phase Ib，Measurement of PK parameters: Time to maximum observed plasma concentration of the study drug (T-max)
Incidence of Treatment-Emergent Adverse Events	3 years	In phase II，Incidence of Treatment-Emergent Adverse Events (TEAEs),A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Pharmacokinetics of Vebreltinib and PLB1004 : Area under the concentration time curve (AUC)	From date of first dose up until 28 days post last dose	In phase Ib，Measurement of PK parameters: Area under the concentration time curve (AUC)

Trial Locations

Locations (1)

Shanghai Pulmonary Hospital; 🇨🇳 Shanghai, Shanghai, China