A Prospective Study of Firmonertinib as First-line Adaptive Therapy Guided by Dynamic ctDNA (MRD) Changes in Locally Advanced or Metastatic EGFR-mutated Non-small Cell Lung Cancer

The pathology is small cell lung cancer (SCLC), including lung cancer with a mixture of SCLC and non-small cell lung cancer (NSCLC);

The patient has received the following treatments:

1. received systemic anti-tumor therapy within 3 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine therapy with anti-tumor indications), etc.;

2. received any investigational drug therapy within 4 weeks before treatment;

3. received high-dose immunosuppressive drugs (systemic glucocorticoids exceeding 10mg/day of prednisone or its equivalent dose) within 4 weeks before treatment;

4. received attenuated live vaccines within 4 weeks before treatment (or plans to receive attenuated live vaccines during the study period);

5. underwent major surgery (such as thoracotomy, thoracotomy, or Kaifu surgery) within 4 weeks before treatment, or has unhealed surgical wounds, ulcers, or fractures.

Subjects with clinically uncontrollable pleural/peritoneal effusion (not requiring drainage of effusion or showing no significant increase in effusion after 3 days of cessation of drainage) may be enrolled;

Subjects with a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia requiring steroid treatment, or any evidence of clinically active ILD;

Subjects who have received chest radiotherapy exceeding 30 Gy within 6 months prior to treatment or palliative radiotherapy of 30 Gy or less within 7 days prior to treatment (palliative radiotherapy for bone or intracranial lesions is allowed);

Subjects who have experienced active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment;

Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation;

Subjects who have not fully recovered from toxicity and/or complications caused by any intervention prior to the start of treatment (i.e., grade ≤1 or baseline, excluding fatigue or alopecia);

Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive);

Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copy number greater than the upper limit of normal in the laboratory department of the research center); Note: Subjects with hepatitis B who meet the following criteria may also be enrolled: 1) HBV viral load \<1000 copies/ml (200 IU/ml) prior to the first dose, and subjects should receive anti-HBV treatment throughout the study drug treatment period to avoid viral reactivation; 2) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV treatment is not required, but close monitoring for viral reactivation is necessary.

Subjects with active HCV infection (HCV antibody positive and HCV-RNA level above the detection limit);

Subjects who have received a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1); Note: Inactivated virus vaccine for seasonal influenza administered via injection is allowed within 30 days prior to the first dose; however, attenuated live influenza vaccine administered intranasally is not allowed.

Pregnant or lactating women;

Subjects with any severe or uncontrollable systemic diseases, such as:

1. significant and symptomatically severe abnormalities in rhythm, conduction, or morphology on resting electrocardiogram, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation;

2. unstable angina, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) classification of ≥ 2;

3. myocardial infarction within 6 months prior to enrollment;

4. poorly controlled blood pressure (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg);

5. history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year prior to the first dose, or current clinically active interstitial lung disease;

6. active tuberculosis;

7. active or uncontrollable infections requiring systemic treatment;

8. clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction;

9. liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;

10. poorly controlled diabetes (fasting blood glucose (FBG) \>10 mmol/L);

11. urine routine test indicating proteinuria ≥++ and confirmed 24-hour urine protein quantitation \>1.0 g;

12. subjects with mental disorders and unable to cooperate with treatment; subjects with medical history or disease evidence, treatment, or laboratory test values that may interfere with trial results, hinder the subject's full participation in the study, or other situations deemed unsuitable for enrollment by the investigator; subjects deemed by the investigator to have other potential risks and are not suitable to participate in this study

What this study is about