Non-Small-Cell Lung Cancer
Conditions
Keywords
NSCLC, Lung Cancer, MET Amplification, EGFR L858R, EGFR Exon 19 Deletion, EGFR
Brief summary
Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure
Detailed description
A Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure
Interventions
DRUGVebreltinib
Subjects will receive Vebreltinib Enteric-coated Capsule orally twice per day (BID).
DRUGPLB1004
Subjects will receive PLB1004 80mg orally once per day (QD).
DRUGPemetrexed plus Carboplatin or Cisplatin
Subjects randomized to the control group received pemetrexed 500 mg/m² + platinum-based chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m²) via intravenous infusion for 4-6 cycles (determined by the investigator) as initial therapy, followed by pemetrexed maintenance therapy (500 mg/m²) until disease progression, intolerable toxicity, initiation of new antitumor therapy, death, loss to follow-up, or other treatment-terminating conditions (whichever occurred first).
Sponsors
Avistone Biotechnology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. At least one measurable lesion as defined by RECIST V1.1. 5. ECOG performance status 0 to 1.
Exclusion criteria
1. There are mutations of ALK or ROS1. 2. Have symptomatic and neurologically unstable central nervous system (CNS) metastases or CNS disease that requires increased steroid doses for control. 3. Before randomization, patients did not recover from any toxicity and/ or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events \[NCI-CTCAE\] v5.0), except for hair loss and irrecoverable permanent radiation damage. 4. Major surgery or had significant traumatic injury within 4 weeks prior to the first dose of the investigational product. 5. Pregnant or nursing women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by BICR | 2 years | Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The objective response rate of the tumor (ORR) | 2 years | Refer to RECIST v1.1, ORR assessed by the investigator and BICR. |
| Duration of Response (DoR) | 2 years | Refer to RECIST v1.1, DoR assessed by the investigator and BICR. |
| The disease control rate (DCR) | 2 years | Refer to RECIST v1.1, DCR assessed by the investigator and BICR. |
| Overall Survival (OS) | 3 years | OS is defined as the time from the date of the first dose until the date of death due to any cause. |
| Objective Response Rate (ORR) in subjects with baseline intracranial metastases | 2 years | Refer to RECIST v1.1，ORR assessed by the investigator and BICR. |
| The Disease Control Rate (DCR) in subjects with baseline intracranial metastases | 2 years | Refer to RECIST v1.1, DCR assessed by the investigator and BICR. |
| Progression-Free Survival (PFS) by the investigator | 2 years | Refer to RECIST v1.1, PFS assessed by the investigator. |
| Progression-Free Survival (PFS) in subjects with baseline intracranial metastases | 2 years | Refer to RECIST v1.1, PFS assessed by the investigator and BICR. |
| Incidence of Treatment-Emergent Adverse Events | 2 years | 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. |
| Plasma concentrations of Vebreltinib and PLB1004 | 2 years | Plasma concentrations of Vebreltinib and PLB1004. |
| Second progression-free survival (PFS2) | 2 years | Investigator-assessed second progression-free survival (PFS2). |
| Assess the Quality of Healthy Living About Patients（EQ-5D-5L） | 2 years | Use the EQ-5D-5L scale to measure patients' quality of healthy living. It has 5 items (Mobility, Self-care, Usual activities, Pain/discomfort, Depression/anxiety). Each item contains 5 levels: 1= no difficulty, 2= slight difficulty, 3= moderate difficulty, 4= serious difficulty, 5= extremely serious difficulty. The higher the score has the worse the health. Then, the score calculation of the European Five-Dimensional Health Scale is based on the calculation formula published by the EuroQol Group. Based on 5 combinations of different severity levels, a score of 0 to 1 is obtained. 0 is the least healthy and 1 is the most healthy. |
| Duration of Response (DoR) in subjects with baseline intracranial metastases | 2 years | Refer to RECIST v1.1, DoR assessed by the investigator and BICR. |
Contacts
Primary ContactLiang Lin
Outcome results
None listed