NSCLC, Adjuvant Drug Therapy, EGFR
Conditions
Brief summary
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.
Interventions
DRUGBefotertinib
Befotertinib 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 (500 mg/m²) and carboplatin (AUC 5), administered every 3 weeks, for a total of 2\ 4 cycles.
Sponsors
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years; 2. 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); 3. 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.; 4. ECOG performance status (PS) score of 0-2; 5. Life expectancy of at least 12 weeks; 6. Ability to swallow oral medications; 7. Adequate organ system function, defined as follows and determined based on investigator judgment: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L 2. Platelets ≥ 100 x 10⁹/L; 3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). Note: Blood transfusions are permitted to achieve the required hemoglobin level; 4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); 5. If no liver metastases: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if liver metastases present: ≤ 5 × ULN; 6. Creatinine ≤1.5 × ULN. If ≥1.5 × ULN, patients remain eligible if the Cockcroft-Gault-calculated creatinine clearance ≥50 mL/min (0.83 mL/s); 8. Female subjects of childbearing potential must have a negative serum pregnancy test within 3 days prior to study drug initiation and agree to use a medically approved highly effective contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 3 months after the last study drug administration; Male subjects with female partners of childbearing potential must be surgically sterilized or agree to use an effective method of contraception during the study period and for 3 months after the last study dose. 9. Voluntarily agree and be capable of adhering to the trial and follow-up procedures. 10. Be able to understand the nature of the trial and complete the written informed consent form.
Exclusion criteria
1. Rare EGFR mutations; 2. Prior treatment with pemetrexed and platinum-based chemotherapy regimens; 3. Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases; 4. 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; 5. Women of childbearing potential with a positive serum pregnancy test within 7 days prior to treatment initiation, pregnant or lactating women, or male and female subjects not using effective contraception or planning pregnancy during treatment and for 3 months post-treatment; 6. Patients who used or require concomitant use of the following drugs within 14 days prior to the first dose or during treatment: drugs associated with QTc prolongation and/or risk of torsades de pointes ventricular tachycardia; strong CYP3A inhibitors or inducers; 7. Patients who underwent major surgery or immunotherapy within 4 weeks prior to the first dose; patients who received radiotherapy within 2 weeks prior to the first dose. 8. Imaging (CT or MRI) demonstrating tumor invasion of major vessels, or a high likelihood of tumor invasion into critical vessels causing fatal hemorrhage during the study period; 9. History of interstitial lung disease, drug-induced interstitial disease, or any clinically evident active interstitial lung disease; presence of idiopathic pulmonary fibrosis identified on baseline CT scan; 10. Other severe acute or chronic medical conditions, including uncontrolled diabetes, medical or psychiatric disorders, or laboratory abnormalities, that in the investigator's judgment may increase study-related risks or interfere with interpretation of study results; 11. Other conditions deemed by the investigator to be unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | From enrollment to the end of treatment at 12 months | It refers to the time from the start of treatment until the tumor progresses or until death occurs for any reason (whichever occurs first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective remission rate | From enrollment to the end of treatment at 12 month | 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 | From enrollment to the end of treatment at 12 months | 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 | From enrollment to the end of treatment at 36 months | Overall survival was defined as the time from participants' treatment to their death due to any cause. |
| adverse event | From enrollment to the end of treatment at 12 months | 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. |
Countries
China
Contacts
Primary ContactShaodong Hong
Outcome results
None listed