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

Non-Small-Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06343064
• Other study ID #: PLB1001/PLB1004-NSCLC-Ib/II-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 13, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Avistone Biotechnology Co., Ltd.
• Contact: Liang Lin
• Phone: +86-10-84148931
• Email: linliang[@]avistonebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Avistone Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).	In phase Ib,Incidence of Treatment-Emergent Adverse Events (TEAEs),	3 years
Primary	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
Primary	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	Pharmacokinetics of Vebreltinib and PLB1004 : Area under the concentration time curve (AUC)	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
Secondary	Pharmacokinetics of Vebreltinib and PLB1004: Maximum plasma concentration of the study drug (C-max)	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
Secondary	Pharmacokinetics of Vebreltinib and PLB1004: Time to maximum plasma concentration of the study drug (T-max)	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
Secondary	Incidence of Treatment-Emergent Adverse Events	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