AC0010 is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral AC0010; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral AC0010; to assess the safety and efficacy of AC0010 in previously treated mutant EGFR in NSCLC patients with EGFR T790M mutation.
Name: AC0010
Description: Stage 1: AC0010 will be administered in escalating dosages in a period of 28-day cycles. Stage 2: AC0010 will be administered twice-daily at RP2D.Type: DrugAC0010
Description: To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: ORR(Objective Response Rate) Time: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 monthsDescription: To assess the duration of response (DOR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: DoR (Duration of Response) Time: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 monthsDescription: To assess the progression-free survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: PFS (Progression-free survival) Time: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 monthsDescription: To assess the disease control rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: DCR (Disease control rate) Time: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 monthsDescription: To assess the overall survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: OS (Overall survival) Time: Every 6 weeks from time of first dose until objective disease progression, then every 3 months until death of lost of follow-up, up to approximately 18 monthsDescription: To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: EORTC QLQ-C30 and LC-13 questionnaire Time: From screening to the end of survival follow-up, which is assessed though study completionDescription: To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure: Adverse events Time: From screening to 30days after end of treatment, which is assessed through study completionSingle Group Assignment
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Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Patients With EGFR T790M Positive Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With EGFR TKIs. --- T790M ---
Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010 in Patients With EGFR T790M Positive NSCLC AC0010 is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. --- T790M ---
The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral AC0010; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral AC0010; to assess the safety and efficacy of AC0010 in previously treated mutant EGFR in NSCLC patients with EGFR T790M mutation. --- T790M ---
To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. DoR (Duration of Response). --- T790M ---
To assess the duration of response (DOR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. PFS (Progression-free survival). --- T790M ---
To assess the progression-free survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. DCR (Disease control rate). --- T790M ---
To assess the disease control rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. OS (Overall survival). --- T790M ---
To assess the overall survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. EORTC QLQ-C30 and LC-13 questionnaire. --- T790M ---
To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. Adverse events. --- T790M ---
To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).. Inclusion Criteria - Stage 1: 1. Patients of either gender, aged from 18 years older to 75. 2. Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC. --- T790M ---
4. Failed to the treatment of EGFRTKI with definite state of T790M, or harbored T790M mutation without the treatment of EGFRTKI. 5. Offer biopsy sample to central lab if failed or without the treatment of EGFRTKI. --- T790M ---
4. Failed to the treatment of EGFRTKI with definite state of T790M, or harbored T790M mutation without the treatment of EGFRTKI. 5. Offer biopsy sample to central lab if failed or without the treatment of EGFRTKI. --- T790M --- --- T790M ---
4. Failed to the treatment of EGFR-TKI and harbored T790M mutation. --- T790M ---
Patients with arbored T790M mutation should be treated with only one kind of medicine or never be treated. --- T790M ---
However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. --- T790M ---
Pre-clinical data demonstrated that AC0010 inhibits T790M. --- T790M ---
It is anticipated that AC0010 may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to previous TKIs. --- T790M ---
It is anticipated that AC0010 may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to previous TKIs. --- T790M --- --- T790M ---
This study will include 2 parts: Stage 1 : Dose-escalation Period with 28-day cycles; Optional Treatment Extension Period starting on Day 29 Stage 2 : Evaluation of activity and safety in patients with the EGFR T790M mutation --- T790M ---