Vebreltinib plus furmonertinib in EGFR-mutated NSCLC with high PD-L1

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an exploratory, two-phase study (phase Ib/II) evaluating a combination of a MET inhibitor and a third-generation EGFR inhibitor as first-line therapy for locally advanced or metastatic NSCLC with EGFR-sensitizing mutations and PD-L1 TPS ≥50%. In phase Ib, two dose levels of vebreltinib (100 mg BID vs 150 mg BID) are tested alongside furmonertinib (80 mg QD) to determine safety and the recommended phase II dose. Phase II will enroll about 37 patients at the RP2D to assess median progression-free survival as the primary endpoint, with secondary endpoints including ORR, DCR, OS, and safety; exploratory aims will explore MET-related biomarkers. The design includes a parallel-cohort dose-escalation with DLT monitoring and predefined criteria for expansion, aiming to overcome primary resistance to EGFR-TKI therapy by dual-pathway blockade.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Voluntarily agree to participate in this study and sign a written informed consent form
2. Age ≥18 years and ≤75 years, regardless of gender
3. Histologically or cytologically confirmed locally advanced (stage IIIB-IIIC), metastatic, or recurrent (stage IV) non-small cell lung cancer, not amenable to surgical resection and definitive concurrent chemoradiotherapy
4. No prior systemic antineoplastic therapy for advanced/metastatic disease Histologically or cytologically confirmed EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R point mutation)
5. Central laboratory-confirmed PD-L1 Tumor Proportion Score (TPS) ≥50%
6. At least one measurable target lesion according to RECIST v1.1 criteria
7. Asymptomatic or locally treated stable brain metastases are allowed.
8. ECOG performance status 0-1
9. Expected survival ≥3 months
10. Adequate organ function

Exclusion Criteria:

1. Histological type of small cell lung cancer or mixed small cell lung cancer
2. Prior treatment with any EGFR-TKI or MET-TKI
3. Presence of ALK fusion positive or ROS1 fusion positive
4. Other active malignant tumors (except completely resected carcinoma in situ, basal cell or squamous cell skin cancer, or tumors with no recurrence for ≥3 years after curative treatment)
5. Major surgery within 4 weeks before first dose (except brain metastasis resection, which requires ≥2 weeks); thoracoscopic biopsy or mediastinoscopy is excluded (requires ≥1 week)
6. Require use of strong CYP3A4 inhibitors or inducers within 1 week before first dose or during the study
7. Uncontrolled systemic diseases
8. Cardiac dysfunction: QTcF \>470ms (average of three ECGs) at screening; NYHA functional class ≥3 or LVEF \<50%
9. Dysphagia, active digestive system disease, or history of major gastrointestinal surgery that may affect drug absorption
10. History of acute or chronic pancreatitis or pancreatic surgery
11. Other conditions deemed unsuitable for participation by the investigator

Where it's running

• The Second Affiliated Hospital of Nanchang University
  Nanchang, Jianxi, China Recruiting

Study contacts

• Study coordinator: Jing Cai, MD, PhD
• Email: cjdl879@163.com
• Phone: +86+0791-86297662

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.