Befotertinib Plus Chemotherapy With an MRD-guided Adaptive Strategy for Treatment Escalation and Response Optimization in EGFR-mutated NSCLC Patients

Inclusion criteria

• Histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer (NSCLC).
• Age ≥18 years, any gender.
• Confirmed EGFR exon 19 deletion or exon 21 (L858R) substitution mutation by central laboratory or site-validated testing assay.
• No prior systemic anti-tumor therapy.
• ECOG performance status 0-2.
• Expected survival ≥12 weeks.
• Able to swallow oral study medication.
• At least one measurable lesion per RECIST 1.1 criteria.
• Adequate organ function as defined below:

• Absolute neutrophil count ≥1.5 × 10^9/L;
• Platelet count ≥100 × 10^9/L;
• Hemoglobin ≥9 g/dL (transfusion allowed);
• Total bilirubin ≤1.5 × ULN;
• ALT/AST ≤2.5 × ULN (≤5 × ULN if liver metastasis);
• Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥45 mL/min by Cockcroft-Gault formula if creatinine >1.5 × ULN.
• Fertile men and women agree to effective contraception during study treatment and for specified time after last dose.

Exclusion criteria

• Receiving other systemic anti-tumor therapy, or plan to combine other systemic anti-cancer agents during study.
• Participated in another investigational drug trial within 4 weeks prior to first study drug; major surgery within 4 weeks; unhealed wound, active ulcer or fracture; radiotherapy within 2 weeks without recovery.
• Severe cardiovascular disease: QTcF ≥450 ms or clinically significant ECG abnormality; uncontrolled hypertension (SBP>160 mmHg or DBP>100 mmHg); congestive heart failure, cardiomyopathy, arrhythmia requiring intervention, unstable angina, myocardial infarction, stroke or TIA within 6 months prior to treatment.
• Uncontrolled active infection including active HBV, HCV, HIV, active syphilis infection judged by investigator. Stable infection without safety risk is permitted.
• History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroids, or active interstitial lung disease.
• Active hemorrhage, clinically significant hemoptysis, high thromboembolic risk or prior severe thromboembolic events unsuitable for study treatment.
• Renal dysfunction with creatinine clearance <45 mL/min; prior intolerable toxicity to pemetrexed; severe hypersensitivity to pemetrexed or its excipients.
• Positive serum pregnancy test within 7 days before treatment, pregnant or breastfeeding women; fertile subjects refusing contraception during study and 3 months after last dose.
• Known severe hypersensitivity to befotertinib, cisplatin, carboplatin or their excipients.
• Any other medical, metabolic, physical or lab abnormality that may compromise subject safety or interfere with study results per investigator judgment.