Advanced Non-small Cell Lung Cancer (NSCLC), EGFR Exon 19 Deletion Mutation, EGFR Exon 21 L858R Mutation, EGFR Exon 21 Mutation
Conditions
Keywords
EGFR sensitive mutation, Minimal Residual Disease, MRD dynamic monitoring, Befotinib, Advanced Non-small Cell Lung Cancer, Targeted therapy plus chemotherapy
Brief summary
This is a multicenter, phase II exploratory clinical trial in untreated patients with EGFR-mutant non-small cell lung cancer (stages IIIB-IV) .All participants will receive oral befotertinib monotherapy for 3 weeks first, then serial minimal residual disease (MRD/MRD) testing is performed to adjust subsequent treatment. Patients with positive MRD will receive 4 cycles of pemetrexed plus platinum chemotherapy; patients with negative MRD will continue single-agent befotertinib. After induction, maintenance therapy will be given according to follow-up MRD results. The primary goal is to evaluate progression-free survival guided by dynamic MRD monitoring, and secondary endpoints include objective response rate, disease control rate, safety and MRD clearance rate.
Interventions
DRUGBefotinib
Oral administration, initial dose 75 mg once daily; dose adjusted to 100 mg once daily based on safety and clinical benefit. Used as induction, single-agent maintenance, or combined with chemotherapy.
This is induction combination chemotherapy for MRD-positive patients after initial befotinib monotherapy. Pemetrexed at 500 mg/m² is given intravenously on Day 1 of each 21-day cycle, combined with either Cisplatin (75 mg/m² IV Day 1) or Carboplatin (AUC 5 IV Day 1) at investigator's discretion based on patient renal function and tolerability, for up to 4 cycles. Standard premedication with folic acid, vitamin B12 and dexamethasone is administered per pemetrexed prescribing guidelines.
Sponsors
Guangzhou University of Traditional Chinese Medicine
Guangdong Provincial Hospital of Traditional Chinese Medicine
Beijing Chest Hospital
Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Sichuan Cancer Hospital and Research Institute
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
First Affiliated Hospital of Xinjiang Medical University
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. Histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer (NSCLC). 2. Age ≥18 years, any gender. 3. Confirmed EGFR exon 19 deletion or exon 21 (L858R) substitution mutation by central laboratory or site-validated testing assay. 4. No prior systemic anti-tumor therapy. 5. ECOG performance status 0-2. 6. Expected survival ≥12 weeks. 7. Able to swallow oral study medication. 8. At least one measurable lesion per RECIST 1.1 criteria. 9. Adequate organ function as defined below: 1. Absolute neutrophil count ≥1.5 × 10\^9/L; 2. Platelet count ≥100 × 10\^9/L; 3. Hemoglobin ≥9 g/dL (transfusion allowed); 4. Total bilirubin ≤1.5 × ULN; 5. ALT/AST ≤2.5 × ULN (≤5 × ULN if liver metastasis); 6. Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥45 mL/min by Cockcroft-Gault formula if creatinine \>1.5 × ULN. 10. Fertile men and women agree to effective contraception during study treatment and for specified time after last dose.
Exclusion criteria
1. Receiving other systemic anti-tumor therapy, or plan to combine other systemic anti-cancer agents during study. 2. 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. 3. 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. 4. Uncontrolled active infection including active HBV, HCV, HIV, active syphilis infection judged by investigator. Stable infection without safety risk is permitted. 5. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroids, or active interstitial lung disease. 6. Active hemorrhage, clinically significant hemoptysis, high thromboembolic risk or prior severe thromboembolic events unsuitable for study treatment. 7. Renal dysfunction with creatinine clearance \<45 mL/min; prior intolerable toxicity to pemetrexed; severe hypersensitivity to pemetrexed or its excipients. 8. 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. 9. Known severe hypersensitivity to befotertinib, cisplatin, carboplatin or their excipients. 10. Any other medical, metabolic, physical or lab abnormality that may compromise subject safety or interfere with study results per investigator judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 48 months after the last participant enrollment,including at least 24 months of follow-up after the last participant is enrolled. | Time from first dose of study treatment to first radiographically confirmed isease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | Including at least 24 months of follow-up after the last participant is enrolled.Participants lost to follow-up will be censored at the last date they were known to be alive. | Defined as the time from first dose of study treatment to death from any cause. |
| Objective response rate (ORR) | including at least 24 months of follow-up after the last participant is enrolled. | Defined as the proportion of participants achieving confirmed complete response (CR) or partial response (PR) per RECIST version 1.1. |
| Disease control rate (DCR) | including at least 24 months of follow-up after the last participant is enrolled. | defined as the proportion of participants achieving confirmed complete response (CR), partial response (PR) or stable disease (SD) per RECIST version 1.1. |
| Time to intolerable toxicity | Including at least 24 months of follow-up after the last participant is enrolled. | Defined as the time from the first dose of study treatment to the first occurrence of treatment-related intolerable adverse event leading to permanent discontinuation of study therapy. |
Countries
China
Contacts
CONTACTXiaoshu Chai, MD
CONTACTYanjuan Zhu, MD
PRINCIPAL_INVESTIGATORXiaoshu Chai, MD
Guangdong Provincial Hospital of Traditional Chinese Medicine
Outcome results
None listed