Patient case: 60-year-old female with gastric cancer; genetic feature: EGFR

Clinical trial: Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer

Summary: 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. Efficiently suppresses the tumor cell with EGFR mutant and has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation.

Detailed description: A Phase I/II, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Ascending Doses of AC0010MA in Patients with Previously Treated EGFRmut and Acquired T790M Mutation Non-Small Cell Lung Cancer.

Eligibility: Inclusion Criteria:
  -  Patients of either gender, aged 18 years or older.
  -  Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
  -  NSCLC patients do not have to have brain metastasis.
  -  At least one measurable disease by CT or MRI, according to RECIST Version 1.1.
  -  Documented evidence of any activating EGFR mutation in the tumor tissue determined by either sequencing or PCR-based technique.
  -  Have undergone or are able to undergo a biopsy of either primary or metastatic tumor tissue within 28 days of dosing of AC0010MA, and have tissue available to send to central lab for further genetic profiling especially the status of T790M.
  -  Life expectancy of at least 3 months.
  -  ECOG performance status of 0 to 1.
  -  Adequate hematological and physiological functions of heart, lung, liver, and kidney, according to definitions given in Appendix D.
  -  Disease progression under at least one treatment with current marketed EGFR TKI therapy for at least 30 days (e.g. erlotinib, or gefitinib, or afatinib). Intervening treatment with chemotherapy after most recent EGFR TKI therapy is permissible with a washout period of 14 days. The washout period for an EGFR TKI (erlotinib, or gefitinib) is at a minimum of 3 days. The washout period for an irreversible EGFR inhibitor (afatinib) is at a minimum of 14 days.
  -  T790M positive patients treated with AZD9291 or CO1686 and who are not tolerant to the AEs of the treatment. The minimum washout period for AZD9291 and CO1686 is 14 days.
  -  Any toxicity related to prior EGFR inhibitor treatment must have been resolved to Grade 1 or less.
  -  Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.
  Exclusion Criteria:
  -  History of interstitial lung disease related to prior EGFR inhibitor therapy.
  -  Symptomatic brain metastases or uncontrollable or unstable brain metastasis.
  -  Positive to HCV or HIV antibody.
  -  Treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal, or immunotherapy) ≤14 days prior to treatment with AC0010MA.
  -  Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 msec (males) or >470 msec (females).
  -  Family history of long QT syndrome.
  -  Implantable pacemaker or implantable cardioverter defibrillator.
  -  Treatment with any Category 1 and 2 drugs.
  -  Those previously treated with AZD9291 or CO1686 and had disease progression.
  -  Non-study related surgical procedures ≤14 days prior to administration of AC0010MA. In all cases, the patient must be sufficiently recovered and stable before AC0010MA administration.
  -  Females who are pregnant or breastfeeding.
  -  Refusal to use adequate contraception for fertile patients (females and males) for 6 months after the last dose of AC0010MA.
  -  Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled psychiatric condition, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism).
  -  Any other reasons for the investigator to consider the patient should not participate in the study.
  -  Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5.

Relevance to patient case: not relevant