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

May 20, 2025 updated by: Avistone Biotechnology Co., Ltd.

A Phase Ib/II Study of Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

156

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200433
        • Recruiting
        • Shanghai Pulmonary Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD
In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.
Drug: Vebreltinib
Phase Ib is a dose escalation study, the initial dose of Vebreltinib is 100mg/150mg/200mg,according to the result of Phase Ib, will confirm the RP2D.
Other Names:
  • Bozitinib
  • PLB1001
Drug: PLB1004
Phase Ib is a dose escalation study, the initial dose of PLB1004 is 80mg/160mg,according to the result of Phase Ib, will confirm the RP2D.
Experimental: Phase II:Cohort 1
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）.
Drug: Vebreltinib
Phase Ib is a dose escalation study, the initial dose of Vebreltinib is 100mg/150mg/200mg,according to the result of Phase Ib, will confirm the RP2D.
Other Names:
  • Bozitinib
  • PLB1001
Drug: PLB1004
Phase Ib is a dose escalation study, the initial dose of PLB1004 is 80mg/160mg,according to the result of Phase Ib, will confirm the RP2D.
Experimental: Phase II:Cohort 2
In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
Drug: Vebreltinib
Phase Ib is a dose escalation study, the initial dose of Vebreltinib is 100mg/150mg/200mg,according to the result of Phase Ib, will confirm the RP2D.
Other Names:
  • Bozitinib
  • PLB1001
Drug: PLB1004
Phase Ib is a dose escalation study, the initial dose of PLB1004 is 80mg/160mg,according to the result of Phase Ib, will confirm the RP2D.
Experimental: Phase II:Cohort 3
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）.
Drug: Vebreltinib
Phase Ib is a dose escalation study, the initial dose of Vebreltinib is 100mg/150mg/200mg,according to the result of Phase Ib, will confirm the RP2D.
Other Names:
  • Bozitinib
  • PLB1001
Drug: PLB1004
Phase Ib is a dose escalation study, the initial dose of PLB1004 is 80mg/160mg,according to the result of Phase Ib, will confirm the RP2D.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Time Frame: 3 years
In phase Ib，Incidence of Treatment-Emergent Adverse Events (TEAEs),
3 years
Incidence of dose-limiting toxicities (DLT) as defined in the protocol.
Time Frame: 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
28 days
Overall Response Rate (ORR）
Time Frame: 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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of Vebreltinib and PLB1004 : Area under the concentration time curve (AUC)
Time Frame: 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)
From date of first dose up until 28 days post last dose
Pharmacokinetics of Vebreltinib and PLB1004: Maximum plasma concentration of the study drug (C-max)
Time Frame: 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)
From date of first dose up until 28 days post last dose
Pharmacokinetics of Vebreltinib and PLB1004: Time to maximum plasma concentration of the study drug (T-max)
Time Frame: 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)
From date of first dose up until 28 days post last dose
Incidence of Treatment-Emergent Adverse Events
Time Frame: 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.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Avistone Biotechnology Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 21, 2024

First Submitted That Met QC Criteria

March 26, 2024

First Posted (Actual)

April 2, 2024

Study Record Updates

Last Update Posted (Actual)

May 21, 2025

Last Update Submitted That Met QC Criteria

May 20, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PLB1001/PLB1004-NSCLC-Ib/II-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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