Non-Small-Cell Lung CancerPhase 1/2DUAL-THRUSTNCT07655622
Vebreltinib Plus Furmonertinib in Patients With EGFR-mutated Advanced Non-small Cell Lung Cancer and High PD-L1 Expression
A Phase 1/2 study testing Vebreltinib and Furmonertinib 80mg in people with Non-Small-Cell Lung Cancer, run by Second Affiliated Hospital of Nanchang University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Small-Cell Lung Cancer
- What is being tested?
- Vebreltinib and Furmonertinib 80mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- 3 Jul 2026to 3 Jun 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- Asymptomatic or locally treated stable brain metastases are allowed.
- ECOG performance status 0-1
- Expected survival ≥3 months
- Adequate organ function
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital of Nanchang University
Nanchang, Jianxi, 330006
Jian Li, PhD, +86-0791-86297662, efyyjs@126.com
Jing Cai, MD, +86-0791-86265873, cjdl879@163.com
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Non-Small-Cell Lung Cancer
- Being tested
- Vebreltinib, Furmonertinib 80mg
- Keywords
- EGFR mutation, PD-L1 high expression, Vebreltinib, Furmonertinib, Non-Small-Cell Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VebreltinibDrug
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
Furmonertinib 80mgDrug
Administered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vebreltinib; Drug: Furmonertinib 80mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1, assessed at 8 weeks after first dose
Measured: Up to 8 weeks from first dose
Phase II: Objective Response Rate (ORR)
Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1
Measured: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Disease Control Rate (DCR)
Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1
Measured: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Overall Survival (OS)
Time from first dose to death from any cause
Measured: From first dose until death from any cause, assessed up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2026
- Study start3 Jul 2026 (estimated)
- Primary completion3 Dec 2027 (estimated)
- Study completion3 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small-Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Nanchang UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Pearl Biotechnology Limited Liability Company
- Responsible party
- Principal investigator, Jing Cai, Second Affiliated Hospital of Nanchang University
- Investigators
- Anwen Liu, PhD, Study chair, Second Affiliated Hospital of Nanchang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07655622
- Sponsor's protocol ID
- IIT-I-2026-021
- Other IDs
- I-MRER[2026] No. 10
- Acronym
- DUAL-THRUST
- Status last verified
- Jun 2026
- First submitted
- 5 Jun 2026
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07655622
- Acronym / sponsor ID
- DUAL-THRUST / IIT-I-2026-021
- Conditions
- Non-Small-Cell Lung Cancer
- Keywords
- EGFR mutation, PD-L1 high expression, Vebreltinib, Furmonertinib, Non-Small-Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Nanchang UniversityUniversity, hospital or other
- Collaborators
- Beijing Pearl Biotechnology Limited Liability Company
- Study start
- 3 Jul 2026 (estimated)
- Primary completion
- 3 Dec 2027 (estimated)
- Study completion
- 3 Jun 2029 (estimated)
- First posted
- 18 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vebreltinib plus Furmonertinib | Experimental | Drug: Vebreltinib, Drug: Furmonertinib 80mgParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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%
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VebreltinibAdministered 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 | Drug | Vebreltinib plus Furmonertinib |
| Furmonertinib 80mgAdministered orally on an empty stomach, 80mg once daily, taken concurrently with Vebreltinib. | Drug | Vebreltinib plus Furmonertinib |
Primary outcome
Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0
Time frame: 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
Phase Ib: Incidence of Grade ≥2 Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Time frame: Up to 8 weeks from first dose
Number of participants experiencing Grade 2 or higher treatment-related adverse events
Phase Ib: Rate of dose reduction, interruption, or discontinuation due to treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Up to 8 weeks from first dose
Proportion of participants requiring dose reduction, interruption, or discontinuation due to treatment-related toxicity
Phase II: Investigator-Assessed Progression-Free Survival (PFS)
Time frame: 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
4 secondary outcomes
Phase Ib: Objective Response Rate (ORR)
Time frame: Up to 8 weeks from first dose
Phase II: Objective Response Rate (ORR)
Time frame: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Disease Control Rate (DCR)
Time frame: From first dose until first documented disease progression or death from any cause, assessed up to 24 months
Phase II: Overall Survival (OS)
Time frame: From first dose until death from any cause, assessed up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Non-Small-Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anwen Liu, PhD study chair
Second Affiliated Hospital of Nanchang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vebreltinib and Furmonertinib 80mg in people with Non-Small-Cell Lung Cancer, run by Second Affiliated Hospital of Nanchang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jing Cai, MD, PhD (+86+0791-86297662, cjdl879@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Incidence of Dose-Limiting Toxicities as assessed by protocol-defined criteria and CTCAE v5.0 (time frame: Up to 28 days from first dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.