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

17 giugno 2026 aggiornato da: Jing Cai, Second Affiliated Hospital of Nanchang University

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

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Patients with advanced NSCLC harboring EGFR mutations and high PD-L1 expression (TPS ≥50%) have primary resistance to third-generation EGFR-TKI monotherapy, with a median PFS of only 3.8-5.0 months, representing an unmet clinical need.

Basic research has shown that PD-L1 can inhibit protein tyrosine phosphatase through a non-immune pathway, leading to sustained MET phosphorylation and induction of MET amplification, which mediates EGFR-TKI resistance.

This study aims to overcome primary resistance by simultaneously blocking the EGFR and MET pathways through the combination of the MET inhibitor Vebreltinib and the third-generation EGFR-TKI furmonertinib.

The study is divided into two phases: the phase Ib dose-escalation phase adopts a parallel cohort design, enrolling two dose groups simultaneously. Each group initially enrolls 3 patients for a 28-day DLT observation period. If DLT ≤1 case, the cohort will be expanded to at least 6 evaluable patients; if DLT ≥2 cases, the cohort will be terminated. The RP2D will be determined comprehensively based on DLT incidence, incidence of grade ≥2 AEs, dose adjustment rate, and 8-week ORR.

The phase II efficacy-expansion phase will use the RP2D, with the primary endpoint being median PFS. It is expected that combination therapy will prolong the median PFS from 4 months in historical data to 8.5 months.

Patients will receive treatment until disease progression, death, withdrawal of informed consent, or intolerable toxicity. Imaging assessments will be performed every 8 weeks, with an additional tumor assessment on day 28 of cycle 1 for phase Ib patients. Safety assessments include adverse events, laboratory tests, electrocardiograms, and echocardiograms, graded according to NCI-CTCAE v5.0.

Tipo di studio

Interventistico

Iscrizione (Stimato)

45

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: Jing Cai, MD, PhD
  • Numero di telefono: +86+0791-86297662
  • Email: cjdl879@163.com

Backup dei contatti dello studio

  • Nome: Liangqian Lv, MD
  • Numero di telefono: +86+0791-86297662
  • Email: 369848857@qq.com

Luoghi di studio

  • Cina
    • Jianxi
      • Nanchang, Jianxi, Cina, 330006
        • Reclutamento
        • The Second Affiliated Hospital of Nanchang University
        • Contatto:
          • Jian Li, PhD
          • Numero di telefono: +86-0791-86297662
          • Email: efyyjs@126.com
        • Contatto:
          • Jing Cai, MD
          • Numero di telefono: +86-0791-86265873
          • Email: cjdl879@163.com
        • Investigatore principale:
          • Anwen Liu, PhD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Vebreltinib plus Furmonertinib
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.
Droga: Vebreltinib
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
Droga: Furmonertinib 80mg
Administered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0
Lasso di tempo: Up to 28 days from first dose
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
Lasso di tempo: Up to 8 weeks from first dose
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
Lasso di tempo: Up to 8 weeks from first dose
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)
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Phase Ib: Objective Response Rate (ORR)
Lasso di tempo: Up to 8 weeks from first dose
Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1, assessed at 8 weeks after first dose
Up to 8 weeks from first dose
Phase II: Objective Response Rate (ORR)
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1
From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Disease Control Rate (DCR)
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1
From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Overall Survival (OS)
Lasso di tempo: From first dose until death from any cause, assessed up to 36 months
Time from first dose to death from any cause
From first dose until death from any cause, assessed up to 36 months

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Exploratory: Objective response rate by baseline MET aberration status as assessed by RECIST 1.1
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Proportion of participants achieving complete response (CR) or partial response (PR), stratified by presence or absence of baseline MET aberrations (MET amplification or MET overexpression)
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
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Proportion of participants achieving CR or PR, stratified by MET overexpression level ( IHC 1+,2+, 3+) measured by immunohistochemistry
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
Lasso di tempo: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Time from first dose to first documented disease progression or death from any cause, whichever occurs first, stratified by presence or absence of baseline MET aberrations (MET amplification or MET overexpression)
From first dose until first documented disease progression or death from any cause, assessed up to 24 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Second Affiliated Hospital of Nanchang University

Collaboratori

Beijing Pearl Biotechnology Limited Liability Company

Investigatori

  • Cattedra di studio: Anwen Liu, PhD, Second Affiliated Hospital of Nanchang University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

3 luglio 2026

Completamento primario (Stimato)

3 dicembre 2027

Completamento dello studio (Stimato)

3 giugno 2029

Date di iscrizione allo studio

Primo inviato

5 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

17 giugno 2026

Primo Inserito (Effettivo)

18 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • IIT-I-2026-021
  • I-MRER[2026] No. 10 (Altro identificatore: Ethics Committee, The Second Affiliated Hospital of Nanchang University)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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