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Report for Clinical Trial NCT02448251

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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)

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.

NCT02448251 Non Small Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

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: Drug

single dose per day (QD) two doses per day (BID)


Primary Outcomes

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.

Secondary Outcomes

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 years

Description: 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 I

Description: 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 I

Description: 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 I

Description: 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 I

Description: 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 I

Description: 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 I

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 T790M

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 ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 61
REST GPC3 WT1 HPGD BRAF PIK3CA TP53 TRIM28 RB1 TRIP13 SLCO2A1 AKT1 CASP8 KRAS TSC1 POU6F2 EWSR1 PRKN LMNA NAB2 TERT TSC2 SLC22A18 BRCA2 PPP2R1B STAT6 STK11 MUC5B ERBB2 TSC2 MBTPS2 BAP1 TSC2 DICER1 PDGFRB PERP EGFR TSC1 DIS3L2 NOTCH3 KEAP1 DICER1 DICER1 WT1 TSC1 C11ORF95 IRF1 CYP2A6 WRN RELA WT1 PTEN SFTPC SFTPA2 ERCC6 TRPV3 TP53 H19 TRIM28 FASLG MAP3K8
Non-small cell lung carcinoma
Genes 3
TP53 TP53 BAP1