Clinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Patients With Advanded NSCLC

Single-arm,Multi-center,Phase II Clinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Mutation-positive Patients With Advanded NSCLC

The study is a single-arm, multi-center, open-label clinical trial. The study aims to expand the sample size based on the fixed dose recommended by the results of previous dose exploration studies in order to further evaluate the study drug's efficacy and safety.

The study is a single-arm, multi-center, open-label clinical trial. The study aims to expand the sample size based on the fixed dose recommended by the results of previous dose exploration studies in order to further evaluate the study drug's efficacy and safety with overall objective tumor response rate (ORR) as the primary efficacy evaluation indicator, and further evaluate subjects' duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and quality of life (QoL). Safety indicators of subjects are further evaluated through adverse events, vital signs and clinical laboratory parameters.

Inclusion Criteria:

1. Aged 18-75 years (including 18 and 75 years old).
2. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent non-small cell lung cancer which cannot receive radical surgery and radiotherapy.
3. The patient has at least one radio graphically (CT, MRI)measurable lesion according to the RECIST criteria for solid tumor response; long-diameter of tumor scanned by CT&MRI ≥10mm, or short-diameter of metastatic cervical lymph nodes≥15mm. With no radiotherapy and biopsy.
4. Patients without CNS metastases or asymptomatic patients with brain metastases. The number of CNS metastases focus≤2, maximum diameter <10mm.
5. Document prove EGFR mutation before treatment of EGFR TKI, or show clinical benefit after treatment of EGFR TKI (PR, CR evaluation according to RECIST or more than half-year SD duration); tumor tissue proved to be EGFR T790M positive mutation by center lab after last treatment.
6. Patients need to undergo biopsy of primary or metastatic tumor tissue and provide pathological sections to site's central lab; otherwise, the patients need to undergo biopsy of primary or metastatic tumor tissue in the screening period and provide pathological sections to the site's central laboratory.
7. Patients who have previously received first-generation EGFR-TKI (erlotinib, gefitinib, ectectin) treatment and developed resistance and are only allowed to have received one chemotherapy regimen (maintenance treatment with the same drug is allowed; but maintenance treatment with a different drug is not allowed), or are positive for primary T790M mutation but have not received treatment or have only received first-line treatment.
8. The patient must have good organ function, including meeting the laboratory test requirements at screening.
9. Patients must recover to ≤Grade 1 (CTCAE v4.03)toxicity from the previous treatment (patients with any grade of hair loss are allowed to enter the study).
10. ECOG score: 0-1 points. No deterioration in the last 2 weeks.
11. Expected survival time:> 12 weeks.
12. Patients who can cooperate with the observation of adverse events and efficacy.
13. Patients or their legal representatives have signed a written informed consent form.

Exclusion Criteria:

1. Acute hepatitis C, chronic hepatitis C and active hepatitis B (positive HBsAg; HBcAb or HBeAb positive and HBV DNA positive).

2. HIV antibody positive, or other acquired, congenital immunodeficiency disease, or a history of organ transplantation.

3. A past history of interstitial lung disease and radiation pneumonia.

4. Clinically significant abnormalities of resting ECG in rhythm, conduction and morphology, such as complete left bundle branch block, Grade II and above heart block, PR interval> 250 ms, or myocardial infarction within the past 6 months; there are risk factors leading to prolongation of QTc interval or increasing arrhythmias, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or medical history of sudden death at an age of < 40 years among the patient's first-degree relatives, and 12-lead ECG QT interval correction Fridericia method (QTcF interval)> 450 ms for male, >470ms for female.

5. The investigator judges based on safety concerns or clinical study process that the patient had any other condition that is prohibited for participation in the clinical study, such as severe infection/inflammation, intestinal obstruction, inability to swallow medication, social/psychological problems, etc.

   With clinically significant electrolyte abnormalities in laboratory tests;

6. In addition to NSCLC, patients who have been diagnosed with another and/or treatment-requiring malignant disease in recent 5 years (this exclusion criterion does not include the following circumstances: completely resected basal cell and squamous cell skin cancer, inert malignant tumor currently requiring no treatment, and any type of completely resected carcinoma in situ).

   Patients who have used high-dose glucocorticoids or other immunosuppressive agents within 1 month prior to screening.

7. Interval time between previous EGFR TKI treatment and AC0010 <8 days or 5 half-time, subject to the long time; Interval time between major surgery /radiotherapy and AC0010 <4 weeks; Patients who are using any drug known to prolong QT interval or known potent CYP3A4 enzyme inducer or inhibitor within 4 weeks before the first dose.

   Patients who have used high-dose glucocorticoids or other immunosuppressive agents within 1 month prior to screening.

8. Patients who have previously administered third-generation EGFR-TKI drugs (e.g.,AZD9291, Avitinib, CO-1686, HM61713, etc.).

9. Patients who have been registered and received the study treatment or withdrawn from the study cannot be enrolled.

10. Pregnant or lactating women.

11. Women with childbearing potential are defined as all women who are physiologically able to have a pregnancy, unless they are using an efficient contraceptive method during treatment and within 7 days after discontinuation of treatment.

12. Patients who are considered by the investigator as inappropriate to participate in the study.