Non-Small-Cell Lung Cancer
Conditions
Keywords
Non-Small-Cell Lung Cancer, EGFR, NSCLC, Lung Cancer, MET Amplified, MET Expression
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.
Interventions
DRUGVebreltinib
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.
DRUGPLB1004
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.
Sponsors
Avistone Biotechnology Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | 3 years | In phase Ib，Incidence of Treatment-Emergent Adverse Events (TEAEs), |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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: 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) |
Countries
China
Contacts
Primary ContactLiang Lin
Outcome results
None listed