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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: EGFR Exon 19 Deletion Mutation; Advanced Non-small Cell Lung Cancer (NSCLC); EGFR Exon 21 Mutation; EGFR Exon 21 L858R Mutation
• Intervention / Treatment: Drug: Befotinib; Drug: Pemetrexed + Cisplatin /Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoshu Chai, MD; Phone Number: +8613570301605; Email: chaixiaoshu@126.com
• Study Contact Backup: Name: Yanjuan Zhu, MD; Phone Number: +8613902260217; Email: zyjsophy@gzucm.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Provincial Hospital of Chinese Medicine
      • Contact: Xiaoshu Chai, MD; Email: chaixiaoshu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Befotertinib with chemotherapy guided by dynamic MRD monitoring; All participants receive oral befotertinib 75 mg once daily for 3 weeks as induction therapy, followed by MRD detection. Treatment is adjusted dynamically based on serial MRD results: MRD-positive patients get 4 cycles of befotertinib plus pemetrexed-platinum chemotherapy; MRD-negative patients continue single-agent befotertinib. Subsequent MRD tests every 12 weeks guide treatment adjustment: patients who have not previously received pemetrexed -platinum chemotherapy and convert to MRD-positive will receive 4 cycles of befotertinib plus pemetrexed-platinum chemotherapy; patients who have previously received pemetrexed-platinum chemotherapy will receive single agent befotertinib if MRD-negative or befotertinib plus pemetrexed maintenance if MRD-positive.Treatment cycles are 21 days, continued until disease progression, intolerable toxicity, withdrawal of consent or death.

Drug: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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.	Up to 48 months after the last participant enrollment,including at least 24 months of follow-up after the last participant is enrolled.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival (OS)	Defined as the time from first dose of study treatment to death from any cause.	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)	Defined as the proportion of participants achieving confirmed complete response (CR) or partial response (PR) per RECIST version 1.1.	including at least 24 months of follow-up after the last participant is enrolled.
Disease control rate (DCR)	defined as the proportion of participants achieving confirmed complete response (CR), partial response (PR) or stable disease (SD) per RECIST version 1.1.	including at least 24 months of follow-up after the last participant is enrolled.
Time to intolerable toxicity	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.	Including at least 24 months of follow-up after the last participant is enrolled.

Collaborators and Investigators

• Sponsor: Guangzhou University of Traditional Chinese Medicine
• Collaborators: Guangdong Provincial Hospital of Traditional Chinese Medicine; Guang'anmen Hospital of China Academy of Chinese Medical Sciences; Beijing Chest Hospital; First Affiliated Hospital of Xinjiang Medical University; Sichuan Cancer Hospital and Research Institute; Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
• Investigators: Principal Investigator: Xiaoshu Chai, MD, Guangdong Provincial Hospital of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): July 5, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: July 12, 2026
• First Submitted That Met QC Criteria: July 12, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Non-small Cell Lung Cancer; Minimal Residual Disease; EGFR sensitive mutation; MRD dynamic monitoring; Befotinib; Targeted therapy plus chemotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm, Residual; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin
• Other Study ID Numbers: ZF2026-214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No