Vebreltinib Plus Furmonertinib in Patients With EGFR-mutated Advanced Non-small Cell Lung Cancer and High PD-L1 Expression

NCT07655622 | Recruiting Phase 1

• 2 other identifiers: IIT-I-2026-021I-MRER[2026] No. 10
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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

Non-Small-Cell Lung Cancer

Keywords

EGFR mutation; PD-L1 high expression; Vebreltinib; Furmonertinib; Non-Small-Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0

  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

  Up to 28 days from first dose

• Phase Ib: Incidence of Grade ≥2 Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  Number of participants experiencing Grade 2 or higher treatment-related adverse events

  Up to 8 weeks from first dose

• Phase Ib: Rate of dose reduction, interruption, or discontinuation due to treatment-related adverse events as assessed by CTCAE v5.0

  Proportion of participants requiring dose reduction, interruption, or discontinuation due to treatment-related toxicity

  Up to 8 weeks from first dose

• Phase II: Investigator-Assessed Progression-Free Survival (PFS)

  Time from first dose to first documented disease progression or death from any cause, assessed according to RECIST v1.1

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

Secondary Outcomes (4)

• Phase Ib: Objective Response Rate (ORR)

  Up to 8 weeks from first dose

• Phase II: Objective Response Rate (ORR)

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

• Phase II: Disease Control Rate (DCR)

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

• Phase II: Overall Survival (OS)

  From first dose until death from any cause, assessed up to 36 months

Other Outcomes (3)

• Exploratory: Objective response rate by baseline MET aberration status as assessed by RECIST 1.1

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

• Exploratory: Objective response rate by MET overexpression level as assessed by RECIST 1.1

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

• Exploratory: Progression-free survival by baseline MET aberration status as assessed by RECIST 1.1

  From first dose until first documented disease progression or death from any cause, assessed up to 24 months

Study Arms (1)

Vebreltinib plus Furmonertinib

EXPERIMENTAL

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.

Drug: Vebreltinib; Drug: Furmonertinib 80mg

Interventions

Vebreltinib DRUG

Administered orally on an empty stomach, 100mg or 150mg twice daily, with an interval of 12±4 hours between morning and evening doses. Dose adjustments are allowed based on toxicity, down to a minimum of 100mg BID

Vebreltinib plus Furmonertinib

Furmonertinib 80mg DRUG

Administered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib.

Vebreltinib plus Furmonertinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate in this study and sign a written informed consent form
• Age ≥18 years and ≤75 years, regardless of gender
• 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
• 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)
• Central laboratory-confirmed PD-L1 Tumor Proportion Score (TPS) ≥50%
• At least one measurable target lesion according to RECIST v1.1 criteria
• Asymptomatic or locally treated stable brain metastases are allowed.
• ECOG performance status 0-1
• Expected survival ≥3 months
• Adequate organ function

You may not qualify if:

• Histological type of small cell lung cancer or mixed small cell lung cancer
• Prior treatment with any EGFR-TKI or MET-TKI
• Presence of ALK fusion positive or ROS1 fusion positive
• 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)
• 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)
• Require use of strong CYP3A4 inhibitors or inducers within 1 week before first dose or during the study
• Uncontrolled systemic diseases
• Cardiac dysfunction: QTcF \>470ms (average of three ECGs) at screening; NYHA functional class ≥3 or LVEF \<50%
• Dysphagia, active digestive system disease, or history of major gastrointestinal surgery that may affect drug absorption
• History of acute or chronic pancreatitis or pancreatic surgery
• Other conditions deemed unsuitable for participation by the investigator

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead
• Beijing Pearl Biotechnology Limited Liability Company: collaborator

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jianxi, 330006, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aflutinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Anwen Liu, PhD

  Second Affiliated Hospital of Nanchang University

  STUDY CHAIR

Central Study Contacts

Jing Cai, MD, PhD

CONTACT

+86+0791-86297662; cjdl879@163.com

Liangqian Lv, MD

CONTACT

+86+0791-86297662; 369848857@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 5, 2026
• First Posted: June 18, 2026
• Study Start: July 3, 2026
• Primary Completion (Estimated): December 3, 2027
• Study Completion (Estimated): June 3, 2029
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)