Non-small cell lung cancer (NSCLC) accounts for over 85% of lung cancers. Approximately 30-40% of East Asian adenocarcinoma patients harbor EGFR mutations. Third-generation EGFR-TKIs achieve a median PFS of about 20 months as first-line therapy, but resistance eventually develops. Studies like MARIPOSA-2 confirm that amivantamab combined with chemotherapy ± lazertinib or immunotherapy regimens (ivucitinib/sintilimab + bevacizumab + chemotherapy) can extend median PFS post-resistance from approximately 4 months to 6-8 months. As a third-generation TKI, befitinib has demonstrated PFS of 16-22 months in both first-line and post-T790M mutation settings. This study aims to further evaluate the feasibility and safety of "pemetrexed + carboplatin followed by befotertinib" for patients resistant to third-generation TKIs.
Age ≥18 years;
Histologically or cytologically confirmed advanced or metastatic non-squamous NSCLC; and prior resistance to third-generation EGFR TKIs, with EGFR-sensitive mutations confirmed via tissue or blood samples (defined as: 19 Del or 21 L858R);
Exclusion of small cell lung cancer (SCLC) or squamous cell carcinoma (SqCC) transformation, and known NSCLC with clear targetable mutations for targeted therapy, such as HER2, MET amplification (GCN ≥ 5), KRAS G12C mutation, BRAF V600E mutation, RET fusion mutation, ALK fusion mutation, NTRK fusion mutation, etc.;
ECOG performance status (PS) score of 0-2;
Rare EGFR mutations;
Prior treatment with pemetrexed and platinum-based chemotherapy regimens;
Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases;
Active hepatitis B (serum HBV DNA ≥10⁴ copies/mL [i.e., 20,000 IU/mL]), hepatitis C virus antibody positive, HIV antibody positive, or treponema pallidum antibody positive;
Single group
Befotertinib
DrugBefotertinib was administered orally at a starting dose of 75 mg per day for 21 days, which could be increased to 100 mg per day if grade 2 or higher thrombocytopenia or headache did not occur within 21 days, or maintained at the original dose (75 mg per day) if grade 2 or higher thrombocytopenia or headache occurred within 21 days.
Pemetrexed + Carboplatin
Drugpemetrexed (500 mg/m²) and carboplatin (AUC 5), administered every 3 weeks, for a total of 2\~4 cycles.
progression free survival
It refers to the time from the start of treatment until the tumor progresses or until death occurs for any reason (whichever occurs first).
objective remission rate
Objective Response Rate was defined as the percentage of participants whose tumor lesions disappear completely or diameters reduced by at least 30% as assessed by RECIST1.1.
Disease control rate
Disease Control Rate was defined as the total percentage of participants except for those with tumor lesions diameters increased by at least 20% as assessed by RECIST1.1.
overall survival
Overall survival was defined as the time from participants' treatment to their death due to any cause.
adverse event
The number of participants with treatment-related adverse events as assessed by CTCAE v4.0 would be recorded and calculated after them participating into the study and taking the experimental drug.
Click on the lead sponsor to view all of their trials.
