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

A Randomized, Controlled, Double-blind, Double-simulated, Multicenter Phase III Clinical Study Evaluating 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.

The purpose of this project is to evaluate progression-free survival (PFS) of D-1553 Tablet versus Docetaxel Injection in subjects with prior standard therapy failure kirsten rat sarcoma viral oncogene (KRAS) G12C mutation positive locally advanced or metastatic non small cell lung cancer (NSCLC), progression-free survival (PFS) as assessed by the Independent Review Committee (IRC) based on RECIST 1.1 was used as the primary endpoint.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Treatment with a KRAS G12C mutation inhibitor or docetaxel at any previous time;

• NSCLC with mutations of other driver genes;

• 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;

• Patients with a previous history of epilepsy；presence of superior vena cava syndrome;

• Cardiovascular system meets any condition:

  1. New York Heart Association (NYHA) Heart Function Grade II and above congestive heart failure;
  2. Severe cardiac arrhythmias requiring medical treatment;
  3. Acute myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass surgery within 6 months prior to enrollment;
  4. Left ventricular ejection fraction (LVEF) <50%;
  5. QT interval (QTcF) at prolonged;
  6. Hypertension that is not effectively controlled;

• 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;

• Severe bone damage due to tumor bone metastasis may occur at present or after randomization;

• 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;

• 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;

• 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;

• 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);
• Human immunodeficiency virus (HIV) antibody positive, liver cirrhosis or active viral hepatitis;
• Active syphilis;
• Patients with renal failure requiring hemodialysis or peritoneal dialysis;
• Poor diabetes control [fasting blood glucose (FBG)> 10 mmol/L];
• 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;
• Pregnant or lactating subjects;
• 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.