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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)

2026年6月17日 更新者：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.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

45

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前：Jing Cai, MD, PhD
  • 電話番号：+86+0791-86297662
  • メール：cjdl879@163.com

研究連絡先のバックアップ

  • 名前：Liangqian Lv, MD
  • 電話番号：+86+0791-86297662
  • メール：369848857@qq.com

研究場所

  • 中国
    • Jianxi
      • Nanchang、Jianxi、中国、330006
        • 募集
        • The Second Affiliated Hospital of Nanchang University
        • コンタクト：
          • Jian Li, PhD
          • 電話番号：+86-0791-86297662
          • メール：efyyjs@126.com
        • コンタクト：
          • Jing Cai, MD
          • 電話番号：+86-0791-86265873
          • メール：cjdl879@163.com
        • 主任研究者：
          • Anwen Liu, PhD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
薬：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
薬：Furmonertinib 80mg
Administered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0
時間枠：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
時間枠：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
時間枠：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)
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
Phase Ib: Objective Response Rate (ORR)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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

その他の成果指標

結果測定
メジャーの説明
時間枠
Exploratory: Objective response rate by baseline MET aberration status as assessed by RECIST 1.1
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Second Affiliated Hospital of Nanchang University

協力者

Beijing Pearl Biotechnology Limited Liability Company

捜査官

  • スタディチェア：Anwen Liu, PhD、Second Affiliated Hospital of Nanchang University

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年7月3日

一次修了 (推定)

2027年12月3日

研究の完了 (推定)

2029年6月3日

試験登録日

最初に提出

2026年6月5日

QC基準を満たした最初の提出物

2026年6月17日

最初の投稿 (実際)

2026年6月18日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月18日

QC基準を満たした最後の更新が送信されました

2026年6月17日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • IIT-I-2026-021
  • I-MRER[2026] No. 10 (その他の識別子：Ethics Committee, The Second Affiliated Hospital of Nanchang University)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

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米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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