Clinical trial · Interventional
Vebreltinib Plus Furmonertinib in Patients With EGFR-mutated Advanced Non-small Cell Lung Cancer and High PD-L1 Expression
A Single-arm, Phase I/II Trial Aimed to Evaluate the Efficacy and Safety of Vebreltinib Plus Furmonertinb as First-line Treatment for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Harboring EGFR Mutations and High PD-L1 Expression
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a single-arm, exploratory phase Ib/II study with a seamless design to evaluate the safety and efficacy of Vebreltinib combined with furmonertinib as first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations (exon 19 deletion or L858R) and PD-L1 TPS ≥50%. In the phase Ib part, 12-16 patients will be enrolled to compare the safety and early efficacy of Vebreltinib 100mg BID versus 150mg BID in combination with furmonertinib 80mg QD, and to determine the recommended phase II dose (RP2D). In the phase II part, 37 patients (including evaluable patients from the RP2D cohort in phase Ib) will receive treatment at the RP2D. The primary endpoint is investigator-assessed median progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Exploratory endpoints will analyze the correlation between baseline MET abnormalities and treatment efficacy.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Non-Small-Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Furmonertinib 80mg | Drug | Firmonertinib | ALIAS |
| Vebreltinib | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Vebreltinib plus Furmonertinib
- description
- Participants with EGFR-sensitizing mutated, PD-L1-high locally advanced or metastatic non-small cell lung cancer (NSCLC) will receive Vebreltinib at the recommended phase 2 dose (RP2D) orally in combination with furmonertinib 80 mg orally once daily, until disease progression or unacceptable toxicity.
- interventionNames
- Drug: Vebreltinib
- Drug: Furmonertinib 80mg
Primary outcomes (4)
- measure
- Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0
- timeFrame
- Up to 28 days from first dose
- description
- Number of participants experiencing dose-limiting toxicities during the dose-escalation phase of the study, based on CTCAE v5.0 grading and protocol-specified DLT criteria
- measure
- Phase Ib: Incidence of Grade ≥2 Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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
References
Publications (0)
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