Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation.
Name: Alflutinib
Type: DrugAlflutinib
Description: Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03
Measure: Incidence and Severity of Treatment-Emergent Adverse Events Time: Adverse events will be collected from baseline until 28 days after the last doseDescription: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out Cmax.
Measure: Maximum Plasma Concentration [Cmax] of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out tmax.
Measure: Peak Plasma Time [tmax] of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day1 to figure out AUC.
Measure: Area under the plasma concentration versus time curve (AUC) of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out terminal rate constant.
Measure: Terminal rate constant of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out clearance.
Measure: Clearance of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out half life.
Measure: Half life of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out volume of distribution.
Measure: Volume of distribution of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out mean resistance time.
Measure: Mean resistance time of single dose Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Cmax of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state Cmax of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: tmax of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state tmax of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Cmin of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: AUC of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state AUC of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Clearance of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state clearance of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Accumulation ratio of Alflutinib and 2 metabolites following multiple doses.
Measure: Accumulation ratio of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Time dependency of Alflutinib and 2 metabolites following multiple doses.
Measure: Time dependency of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Evaluation of objective response rate assessed by RECIST 1.1
Measure: Objective response rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 monthsDescription: Duration of response assessed by RECIST 1.1
Measure: Duration of response of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 monthsDescription: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival
Measure: Progression free survival of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 monthsDescription: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease progression rate
Measure: Disease progression rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 monthsDescription: Clinical benefit rate was calculated by adding up complete remission, partial remission and stabilization of disease assessed by RECIST 1.1
Measure: Clinical benefit rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 monthsSingle Group Assignment
There are 3 SNPs
4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) 5. Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy). --- L858R ---
4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) 5. Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy). --- L858R --- --- L861Q ---
Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Alflutinib in Advanced Non Small Cell Lung Cancer Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. --- T790M ---
This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation. --- T790M ---