AC0010MA is a new, irreversible, Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor. Aim at local advanced or metastatic non-small cell lung cancer patients with EGFR mutation or T790M drug-resistant mutation. The molecular mechanism: by irreversible combining the EGFR-RTKs ATP binding site of cell, selectively suppress the activities of EGFR tyrosine kinase phosphorylation, block the signal transduction pathway of EGFR and inhibit the function of ras/raf/MAPK downstream, thus block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010MA Maleate Capsules has three characters: 1. Irreversible binding to EGFR; 2. Effectively suppresses the tumor cell with EGFR mutant while has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation.
Name: AC0010MA
Description: Following Phase I, a protocol amendment will be submitted to the IND to specify the selected dose and dose justification to be used in Phase II.Type: Drugsingle dose per day (QD) two doses per day (BID)
Description: To determine the safety and tolerability and to establish the maximum tolerated dose (MTD) of AC0010MA by incidence of dose limiting toxicity (DLT), defined as Grade 3 or 4 adverse events (AEs) and clinical lab abnormalities occurring within the first 28 days of treatment.
Measure: Safety and tolerability, and the maximum tolerated dose (MTD) of AC0010MA determined by incidence of dose limiting toxicity (DLT) Time: Within the first 28 days of treatment.Description: To characterize tumor response (objective response rate, ORR) and duration of response of AC0010MA as a criterion for further development of AC0010MA in this patient population.
Measure: Evaluation of tumor response and duration of response of AC0010MA ((objective response rate, ORR) Time: within the time frame of every 8 weeks (2 cycles) for up to 3 yearsDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Maximum plasma concentration (Cmax) of AC0010MA Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Time to Cmax Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Terminal half-life (t1/2) Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Area under the plasma concentration-time curve Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Volume of distribution (V/F) Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IDescription: To evaluate pharmacokinetic parameter of AC0010MA
Measure: Plasma Concentration (CL/F) Time: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase IAllocation: Non-Randomized
Single Group Assignment
There is one SNP
A Phase I, Multicenter, Open-Label Safety, Pharmacokinetic and Preliminary Efficacy Study of Wild-type Sparing EGFR Inhibitor, AC0010MA, in Adult Patients With Previously Treated EGFRmut and Acquired T790M Mutation Non-Small Cell Lung Cancer (NSCLC). --- T790M ---
Aim at local advanced or metastatic non-small cell lung cancer patients with EGFR mutation or T790M drug-resistant mutation. --- T790M ---
AC0010MA Maleate Capsules has three characters: 1. Irreversible binding to EGFR; 2. Effectively suppresses the tumor cell with EGFR mutant while has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation. --- T790M ---
4. Has documented evidence of an activating EGFR mutation in the tumor tissue determined by either sequencing or PCR-based technique (Part 1). 5. For Part 1 only: subjects with a positive T790M mutation are preferred, but not required. --- T790M ---
Confirmation of T790M mutation status will be determined from an archived tumor tissue sample or fresh tumor tissue sample obtained via biopsy if archived tissue is not available. --- T790M ---
In Part 2, subjects must have a confirmed, positive T790M EGFR mutation (acquired T790M EGFR mutation or "de novo" T790M EGFR mutation). --- T790M ---
In Part 2, subjects must have a confirmed, positive T790M EGFR mutation (acquired T790M EGFR mutation or "de novo" T790M EGFR mutation). --- T790M --- --- T790M ---
In Part 2, subjects must have a confirmed, positive T790M EGFR mutation (acquired T790M EGFR mutation or "de novo" T790M EGFR mutation). --- T790M --- --- T790M --- --- T790M ---
9. Has documented disease progression while receiving at least 30 days of treatment with a currently approved EGFR tyrosine kinase inhibitor (TKI) (e.g., erlotinib, gefitinib or afatinib) with intervening treatment after most recent EGFR TKI therapy (not required for "de novo" T790M EGFR mutation). --- T790M ---