이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

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

2026년 6월 17일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

45

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Jing Cai, MD, PhD
  • 전화번호: +86+0791-86297662
  • 이메일: cjdl879@163.com

연구 연락처 백업

  • 이름: Liangqian Lv, MD
  • 전화번호: +86+0791-86297662
  • 이메일: 369848857@qq.com

연구 장소

  • 중국
    • Jianxi
      • Nanchang, Jianxi, 중국, 330006
        • 모병
        • The Second Affiliated Hospital of Nanchang University
        • 연락하다:
          • Jian Li, PhD
          • 전화번호: +86-0791-86297662
          • 이메일: efyyjs@126.com
        • 연락하다:
        • 수석 연구원:
          • Anwen Liu, PhD

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: 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
의약품: Furmonertinib 80mg
Administered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0
기간: 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
기간: 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
기간: 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)
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Phase Ib: Objective Response Rate (ORR)
기간: 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)
기간: 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)
기간: 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)
기간: 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

기타 결과 측정

결과 측정
측정값 설명
기간
Exploratory: Objective response rate by baseline MET aberration status as assessed by RECIST 1.1
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Second Affiliated Hospital of Nanchang University

협력자

Beijing Pearl Biotechnology Limited Liability Company

수사관

  • 연구 의자: Anwen Liu, PhD, Second Affiliated Hospital of Nanchang University

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 3일

기본 완료 (추정된)

2027년 12월 3일

연구 완료 (추정된)

2029년 6월 3일

연구 등록 날짜

최초 제출

2026년 6월 5일

QC 기준을 충족하는 최초 제출

2026년 6월 17일

처음 게시됨 (실제)

2026년 6월 18일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 18일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 6월 17일

마지막으로 확인됨

2026년 6월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

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

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

비소세포폐암에 대한 임상 시험

Vebreltinib에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Gabon

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

구독하다