This phase I trial with dose-escalation stage and dose-expansion stage is the first-in-human study of FCN-411, a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of FCN-411 monotherapy in EGFR-positive mutation non-small cell lung cancer chinese patients. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the anti-tumor activities of FCN-411.
Name: FCN-411
Description: This is a five parts study to determine the pharmacokinetics of FCN-411 administered orally at five dose levels (4 mg Cohort 1、8mg Cohort 2、 16mg Cohort 3、24mg Cohort 4 and 32mg Cohort 5) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).Type: Drugfcn-411 4mg fcn-411 8mg fcn-411 16mg fcn-411 24mg fcn-411 32mg
Description: Cmax of FCN-411 following single dose.
Measure: Cmax of FCN-411 following single dose. Time: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.Description: AUC of FCN-411 After Single Dosing.
Measure: AUC of FCN-411 following single dose. Time: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.Description: Cmax of FCN-411 After multiple dosing.
Measure: Cmax of FCN-411 following multiple dosing. Time: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.Description: AUC of FCN-411 After Multiple Dosing.
Measure: AUC of FCN-411 following multiple dosing. Time: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.Description: Tmax of FCN-411 following single dose.
Measure: Tmax of FCN-411 following single dose. Time: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.Description: Tmax of FCN-411 following multiple dosing.
Measure: Tmax of FCN-411 following multiple dosing. Time: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.Description: t1/2 of FCN-411 following single dose.
Measure: t1/2 of FCN-411 following single dose. Time: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.Description: t1/2 of FCN-411 following multiple dosing
Measure: t1/2 of FCN-411 following multiple dosing Time: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.Allocation: Non-Randomized
Parallel Assignment
There is one SNP
3. Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ) and T790M status by biopsy sample or optical microscopy. --- T790M ---
Exclusion Criteria: 1. Treatment with any of the following: 1. Treatment with an EGFR TKI within 14 days or about 5x half-life, whichever is the longer, of the first dose of study drug; 2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 14 days of the first dose of study treatment; 3. Major surgery within 4 weeks of the first dose of study treatment; 4. Systemic irradiation including whole brain irradiation; 5. Previously treated by EGFR-TKI for T790M (for example Osimertinib). --- T790M ---