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

NCT06343064 | Recruiting Phase 1

• 1 other identifier: PLB1001/PLB1004-NSCLC-Ib/II-01
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-Small-Cell Lung Cancer

Keywords

Non-Small-Cell Lung Cancer; EGFR; NSCLC; Lung Cancer; MET Amplified; MET Expression

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

  In phase Ib，Incidence of Treatment-Emergent Adverse Events (TEAEs),

  3 years

• Incidence of dose-limiting toxicities (DLT) as defined in the protocol.

  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）

  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 Outcomes (4)

• Pharmacokinetics of Vebreltinib and PLB1004 : 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)

  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)

  From date of first dose up until 28 days post last dose

• Incidence of Treatment-Emergent Adverse Events

  3 years

Study Arms (4)

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

EXPERIMENTAL

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

Drug: Vebreltinib; Drug: PLB1004

Phase II:Cohort 1

EXPERIMENTAL

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; Drug: PLB1004

Phase II:Cohort 2

EXPERIMENTAL

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; Drug: PLB1004

Phase II:Cohort 3

EXPERIMENTAL

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; Drug: PLB1004

Interventions

Vebreltinib DRUG

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.

Also known as: Bozitinib, PLB1001

Phase II:Cohort 1; Phase II:Cohort 2; Phase II:Cohort 3; Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD

PLB1004 DRUG

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.

Phase II:Cohort 1; Phase II:Cohort 2; Phase II:Cohort 3; Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Avistone Biotechnology Co., Ltd.: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Liang Lin

CONTACT

+86-10-84148931; linliang@avistonebio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: April 2, 2024
• Study Start: June 13, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

CN (1)