D-1553 Tablet Versus Docetaxel Injection for KRAS G12C Mutation-positive Locally Advanced or Metastatic Non-small Cell Lung Cancer After Prior Standard Therapy Failure

Prior treatment

• Treatment with a KRAS G12C mutation inhibitor or docetaxel at any previous time;
• Patients with a previous history of epilepsy；presence of superior vena cava syndrome;
• Subjects with stroke or other severe cerebrovascular disease within 6 months before enrollment;
• History of deep vein thrombosis or any other serious thromboembolism within 3 months prior to enrollment;
• History of interstitial lung disease, radiation pneumonitis, and immune-associated pneumonia previously treated with steroids, Or active non-infectious pneumonia with interstitial lung disease, radiation pneumonia, and immune-related pneumonia during the screening period, Presence of active tuberculosis, pneumoconiosis or grade 2 other type of pneumonia, or pulmonary function tests confirming severely impaired pulmonary function;
• Known impaired gastrointestinal (GI) function or known GI diseases that may significantly affect the absorption or metabolism of oral drugs.
  • Previous history of major surgery in the digestive tract (esophagus, gastrointestinal tract) that may alter the absorption or inability to swallow drugs in the study treatment;
• Previous history of organ transplantation or readiness to undergo organ transplantation;
• Weight of \<40 kg and BMI of \<18.5 kg/m2, or weight loss of\> 5% within 3 months before enrollment;
• Major surgical treatment or significant traumatic injury within 4 weeks prior to the first dose of this study;
• Receiving palliative radiotherapy with local lesions within 2 weeks before the first dose of this study;

Other illness

• Symptomatic or progressive aggravation of central nervous system metastasis or cancerous meningitis. Subjects with a history of brain metastasis may be considered to be selected if they are clinically stable;
• Active or uncontrolled serious infection (≥grade 2 infection of common toxicity criteria for adverse events (CTC AE)) or fever of unknown origin \> 38.5°C;
• Human immunodeficiency virus (HIV) antibody positive, liver cirrhosis or active viral hepatitis;
• Patients with renal failure requiring hemodialysis or peritoneal dialysis;
• With the combination of other primary malignancies
• Serious mental or mental illness or history of substance abuse or serious alcohol abuse;
• Known allergy to the investigational medicinal product or any ingredient in the formulation;
• Any other significant clinical abnormality or disease that the investigator considers poses a risk to subject safety or interferes with the medication and evaluation of the clinical study.

Lab values

• Cardiovascular system meets any condition:
  • New York Heart Association (NYHA) Heart Function Grade II and above congestive heart failure;
  • Severe cardiac arrhythmias requiring medical treatment;
  • Acute myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass surgery within 6 months prior to enrollment;
  • Left ventricular ejection fraction (LVEF) \<50%;
  • QT interval (QTcF) at prolonged;
  • Hypertension that is not effectively controlled;
• Toxicity of previous antitumor therapy, except alopecia, pigmentation, clinically insignificant laboratory abnormalities) has not recovered to grade 1, and peripheral nerve toxicity has not recovered to grade 2 ( CTCAE v5.0);
• Poor diabetes control \[fasting blood glucose (FBG)\> 10 mmol/L\];

Other

• NSCLC with mutations of other driver genes;
• Severe bone damage due to tumor bone metastasis may occur at present or after randomization;
• The third space effusion (including pleural effusion, abdominal effusion or pericardial effusion), poor clinical control or the need for local symptomatic treatment such as puncture and drainage;
• Active syphilis;
• Pregnant or lactating subjects;

• Voluntary participation in the study and sign of written informed consent after full informed consent, willing and able to comply with the study procedures and requirements specified in the protocol;
• Age greater than or equal to 18 years old; male and female; eastern cooperative oncology group performance status (ECOG) score 0-1; expected survival period greater than or equal to 3 months;
• Pathologically confirmed locally advanced, unresectable and / or metastatic non-small cell lung cancer (stage III b / III c / IV of american joint committee on cancer (AJCC) 8th);
• Subjects must provide adequate and qualified tumor tissue specimens (surgical resection samples or puncture / biopsy tissue samples within 2 years prior to screening) for confirmation of the KRAS G12C mutation in the central laboratory;
• Disease progression or toxicity after previous treatment with first-line anti-PD-1 / PD-L1 and platinum-containing chemotherapy is not tolerated.Subjects who have clear medical reasons and can not tolerate anti-PD-1 / PD-L1 therapy or platinum-containing chemotherapy;
• Having at least one target lesion according to RECIST 1.1;
• Good function of the major organs;
• Female subjects of childbearing age should agree that contraception must be used during the study and within 6 months after the end of the study; the serum pregnancy test is negative within 7 days before study enrollment and must be non-lactating subjects; male subjects should agree that contraception must be used during the study and within 6 months after the end of the study period.