Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI (KYLIN-1)

Avistone Biotechnology

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Non-Small-Cell Lung Cancer

Treatments: Drug: PLB1004; Drug: Vebreltinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06343064

PLB1001/PLB1004-NSCLC-Ib/II-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 156 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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156 participants in 4 patient groups

Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD

Experimental group

Description:

In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.

Treatment:

Drug: Vebreltinib

Drug: PLB1004

Phase II:Cohort 1

Experimental group

Description:

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）.

Treatment:

Drug: Vebreltinib

Drug: PLB1004

Phase II:Cohort 2

Experimental group

Description:

In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.

Treatment:

Drug: Vebreltinib

Drug: PLB1004

Phase II:Cohort 3

Experimental group

Description:

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）.

Treatment:

Drug: Vebreltinib

Drug: PLB1004