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

Обзор

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.

Вмешательства

• Препарат Befotinib
  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.
• Препарат Pemetrexed + Cisplatin /Carboplatin
  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.

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: Up to 48 months after the last participant enrollment,including at least 24 months of follow-up after the last participant is enrolled.]

Вторичные конечные точки (4)

• Median Overall Survival (OS) [Срок оценки: 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.]
• Objective response rate (ORR) [Срок оценки: including at least 24 months of follow-up after the last participant is enrolled.]
• Disease control rate (DCR) [Срок оценки: including at least 24 months of follow-up after the last participant is enrolled.]
• Time to intolerable toxicity [Срок оценки: Including at least 24 months of follow-up after the last participant is enrolled.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Guangdong Provincial Hospital of Chinese Medicine — Гуанчжоу

Идентификаторы

NCT: NCT07709585 · ZF2026-214

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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