A Study of Vebreltinib and Platinum-Containing Double Agents in Subjects With MET-Positive

NCT06930794 | Recruiting Phase 3 DMC

• 1 other identifier: PLB1001-IIIb-NSCLC-02
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

This study is an open-label, randomized, controlled, multicenter Phase IIIb clinical study, aiming to evaluate the efficacy, safety, and tolerability of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy compared with platinum-based doublet chemotherapy in treating subjects with locally advanced or metastatic non-squamous NSCLC who have not received previous systemic treatment and MET-positive. The target population of this study is subjects with histologically confirmed locally advanced or metastatic non-squamous NSCLC who have not received previous systemic anti-tumor treatment and MET-positive( MET Amplification or Overexpression). This study adopts an enrichment design. The enriched population is those with MET GCN ≥ 6, and the overall population is those with MET GCN ≥ 4. This study consists of two parts: the lead-in period (Part 1) and the randomized controlled period (Part 2). Both the lead-in period (Part 1) and the randomized controlled period (Part 2) will include a screening period (from Day -28 to Day -1), a treatment period (until the termination of treatment), and a follow-up period (including safety follow-up and survival follow-up).

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Introductory phase-Dose-limiting toxicity (DLT) Incidence of DLT events during the observation period

  laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and the Eastern United States Collaborative Oncology Group (ECOG) clinically significant abnormal values in physical status (PS).To evaluated DLT events during the observation period.

  1 year

• Incidence and severity of adverse events (AEs) .

  laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and the Eastern United States Collaborative Oncology Group (ECOG) clinically significant abnormal values in physical status (PS).

  1 year

• Introductory phase-Recommended dosage for MTD and/or co-administration.

  Confirm Recommended dosage for MTD and/or co-administration.

  1 year

• Randomized control period-Progression-free survival (PFS) as assessed by the Blinded Independent Center Review Board (BICR) according to RECIST V1.1 in the MET GCN ≥6-enriched population.

  Progression Free Survival is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD or death due to any cause.

  4 years

• Randomized control period-Progression-free survival (PFS) as assessed by BICR according to the criteria for evaluating the efficacy of solid tumors (RECIST V1.1) in the full MET GCN ≥4 population.

  Progression Free Survival is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD or death due to any cause.

  4 years

Secondary Outcomes (23)

• Introductory phase-Objective Response Rate (ORR) as assessed by the investigator according to RECIST V1.1.

  2 years

• Introductory phase-Duration of Remission (DoR) as assessed by the investigator according to RECIST V1.1.

  2 years

• Introductory phase-Disease control rate (DCR) as assessed by the investigator according to RECIST V1.1.

  2 years

• Introductory phase-Progression-free survival (PFS), 6-month PFS rate as assessed by the investigator according to RECIST V1.1.

  2 years

• Introductory phase-6-month overall survival (OS) rate as assessed by the investigator according to RECIST V1.1.

  2 years

Other Outcomes (5)

• Introductory phase-Drug resistance related mechanism.

  4 years

• Randomized control period- Second progression-free survival (PFS2) as assessed by the investigators.

  4 years

• Randomized control period- Subject Health-Related Quality of Life (HRQoL) assessment: European Five Dimensional Health Scale (EQ-5D-5L).

  4 years

Study Arms (2)

The experimental group will receive the treatment regimen of Vebreltinib combined with platinum-base

EXPERIMENTAL

Vebreltinib: Each cycle is 3 weeks (21 days). It is administered orally twice a day (BID), and the dosage level depends on the cohort assignment. Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on the first day (D1) of each cycle. Pemetrexed at a dose of 500 mg/m² plus a platinum agent (carboplatin with an area under the curve (AUC) of 5 or cisplatin at a dose of 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment. After that, it is switched to pemetrexed (500 mg/m²) given by intravenous infusion as the maintenance treatment.

Drug: Vebreltinib combined with platinum-based doublet chemotherapy.

The comparator group will receive the platinum-based doublet chemotherapy regimen.

ACTIVE COMPARATOR

Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on the first day (D1) of each cycle. Pemetrexed at a dose of 500 mg/m² plus a platinum agent (carboplatin with an area under the curve (AUC) of 5 or cisplatin at a dose of 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment. After that, it is switched to pemetrexed (500 mg/m²) given by intravenous infusion as the maintenance treatment.

Drug: platinum-based doublet chemotherapy.

Interventions

platinum-based doublet chemotherapy. DRUG

Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on the first day (D1) of each cycle. Pemetrexed at a dose of 500 mg/m² plus a platinum agent (carboplatin with an area under the curve (AUC) of 5 or cisplatin at a dose of 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment. After that, it is switched to pemetrexed (500 mg/m²) given by intravenous infusion as the maintenance treatment.

The comparator group will receive the platinum-based doublet chemotherapy regimen.

Vebreltinib combined with platinum-based doublet chemotherapy. DRUG

Vebreltinib: Each cycle is 3 weeks (21 days). It is administered orally twice a day (BID), and the dosage level depends on the cohort assignment. Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on the first day (D1) of each cycle. Pemetrexed at a dose of 500 mg/m² plus a platinum agent (carboplatin with an area under the curve (AUC) of 5 or cisplatin at a dose of 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment. After that, it is switched to pemetrexed (500 mg/m²) given by intravenous infusion as the maintenance treatment.

The experimental group will receive the treatment regimen of Vebreltinib combined with platinum-base

Eligibility Criteria

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

You may qualify if:

• male or female subjects ≥ 18 years of age at the time of signing ICF.
• histologically or cytologically confirmed diagnosis of non-radical, locally advanced (Stage IIIB and IIIC) or metastatic (Stage IV) non-squamous cell type NSCLC (refer to the American Joint Committee on Cancer \[AJCC\] Lung Cancer Stages, 8th edition for lung cancer staging criteria).
• Part 1 (introductory stage)Subjects with MET-positive (MET amplification or MET overexpression) tumors will be enrolled. MET amplification is defined as the presence of MET amplification confirmed by second-generation sequencing (NGS) or fluorescence in situ hybridization (FISH) with a mean MET GCN ≥ 4 cells/cell or MET/CEP7 ≥ 2. MET overexpression is defined as c-Met showing strong positive (3+) staining in ≥50% of tumor cells as determined by immunohistochemistry (IHC) (central laboratory results). And subjects are required to provide sufficient tumor tissue (archived or fresh samples) for retrospective analysis in the central laboratory (see Laboratory Manual) to support the development of concomitant diagnostic reagents required for the marketing of Vebreltinib. Part 2 (Randomized Control Phase) MET amplification is defined as subjects' tumor tissue (archived or fresh samples) with an average MET GCN ≥ 4 cells/cell or MET/CEP7 ≥ 2 as confirmed by fluorescence in situ hybridization (FISH) in the central laboratory, and subjects will be required to provide sufficient tumor tissue (archived or fresh samples) for retrospective assay analysis by a central laboratory (see Laboratory Manual). Laboratory Manual) to support the development of concomitant diagnostic reagents required for the marketing of Vebreltinib.
• Part 1 (Lead-in Period): Documented evidence confirms that the tumor tissue specimen tested negative for sensitive epidermal growth factor receptor (EGFR) mutations (including exon 19 deletion, exon 21 L858R or L861Q mutations, exon 18 G719X mutations, exon 20 S768I/T790M mutations, or exon 20 insertion mutations), ALK fusion-negative, ROS1 fusion-negative, and MET exon 14 skipping mutation-negative. Additionally, if the subject has already undergone testing for BRAF V600E mutation, NTRK fusion, RET fusion, or ERBB2 (HER-2) mutation, the results must be negative.
• Part 2 (Randomized Controlled Period): Documented evidence confirms that the tumor tissue specimen tested negative for sensitive EGFR mutations (including exon 19 deletion, exon 21 L858R or L861Q mutations, exon 18 G719X mutations, exon 20 S768I/T790M mutations, or exon 20 insertion mutations), ALK fusion-negative, ROS1 fusion-negative, and MET exon 14 skipping mutation-negative. Additionally, if the subject has already undergone testing for BRAF V600E mutation, KRAS mutation, NTRK fusion, RET fusion, or ERBB2 (HER-2) mutation, the results must be negative.
• no prior systemic therapy for locally advanced or metastatic non-squamous NSCLC. Note: Subjects are permitted to receive neoadjuvant/adjuvant therapy as long as the relevant therapy has been completed for at least 6 months prior to disease diagnosis of locally progressive or metastatic tumor.
• at least one measurable target lesion as defined by the Response to Criteria for Evaluation of Efficacy in Solid Tumors (RECIST) V1.1 criteria (see Chapter 10.4).
• ECOG PS ≤ 1.
• expected survival ≥ 12 weeks as determined by the investigator.
• good organ function as determined by medical evaluation (within 7 days prior to first study dose), including:
• Good hematologic status, defined as absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 x 10\^9/L. No platelet transfusions within 3 days prior to the test, no red blood cell transfusions within 14 days prior to the test, and no hematopoietic growth factor therapy within 7 days prior to the test (polyethylene glycolated granulocyte colony-stimulating factor \[G-CSF\] or erythropoietin \[EPO\] within 14 days prior to testing).
• Good hepatic function, defined as serum TBIL ≤ 1.5 x ULN (TBIL ≤ 3 x ULN and direct bilirubin \[DBIL\] ≤ 1.5 x ULN in subjects known to have Gilbert's syndrome), serum ALT/AST ≤ 2.5 x ULN (≤ 5.0 x ULN for subjects with confirmed liver metastases) .
• The organ function is well-determined by medical evaluation (within 7 days prior to the first study drug administration), including:
• Good renal function , defined as: creatinine clearance rate ≥50 mL/min (≥60 mL/min for those receiving cisplatin, calculated using the Cockcroft-Gault formula).
• Good coagulation function, defined as (including when receiving anticoagulation): prothrombin time (PT) \< 1.5 x ULN and activated partial thromboplastin time (APTT) \< 1.5 x ULN If subjects are receiving anticoagulant therapy, they must have received a stabilized dose of anticoagulant for at least 1 month prior to the first study dose.

You may not qualify if:

• has participated in another therapeutic clinical trial within 28 days prior to the first study dose.
• have undergone major surgery within 28 days prior to the first study dose or anticipate the need for major surgery during the study period. Diagnostic procedures such as thoracoscopic biopsy and mediastinoscopy may be enrolled 7 days after the procedure. No waiting period is required after implantable infusion port and catheter placement.
• lung field or whole brain radiotherapy within 28 days prior to first study dose or palliative localized radiotherapy within 14 days prior to first study dose.
• have received a proprietary Chinese medicine with an antitumor indication within 1 week prior to the first study dose. Has received local antitumor drug therapy (e.g., thoracic or abdominal perfusion, etc.) within 14 days or 5 half-lives, whichever is shorter, prior to the first study dose.
• a history of another primary malignancy diagnosed or requiring treatment within the past 3 years (with the exception of localized basal cell carcinoma of the skin or squamous cell carcinoma of the skin, which has been adequately treated, or any other carcinoma in situ currently in complete remission)
• toxicity from prior therapy that has not returned to ≤ Grade 1 or baseline levels (as assessed by NCI-CTCAE v5.0), except for alopecia, skin pigmentation, and any other toxicity that is assessed by the investigator to be stable and does not affect the safety of participation in this study
• presence of clinically symptomatic CNS metastases. Note: Subjects with symptomatic CNS metastases may be enrolled in the study after they have been treated and their symptoms are controlled, have no lesion progression for at least 2 weeks during the Screening Period as confirmed by clinical and imaging studies, and have not had an increase in their steroid dose (\<10 mg/day of prednisolone or its equivalent) for the management of CNS symptoms in the 4 weeks prior to the first study dose.
• Those with combined carcinomatous meningitis or meningeal spread or spinal cord compression were not eligible for enrollment, regardless of whether they had clinical symptoms.
• subjects with poorly controlled clinical third space effusions, including but not limited to pleural effusions, abdominal effusions, or pericardial effusions, who, in the judgment of the investigator, are not suitable for enrollment.
• presence of severe cardiovascular or cerebrovascular disease, including but not limited to:
• Mean QT interval (QTcF) corrected by the Fridericia formula from three ECG examinations at rest \> 470 ms.
• Symptomatic heart failure with a New York Heart Association (NYHA) cardiac function classification of II or higher (see Chapter 10.6).
• Echocardiographic (ECHO) assessment showing a baseline left ventricular ejection fraction (LVEF) below the lower limit of institutional normal (LLN) or \<50%.
• Any clinically significant rhythmic, conduction, or morphologic abnormality as demonstrated by resting ECG results, such as complete left bundle branch block, third-degree heart block, and ventricular arrhythmias requiring antiarrhythmic drug therapy.
• Presence of any factor that increases the risk of QTc prolongation or the risk of arrhythmia, such as heart failure, Severe hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or use of any comorbid medication known to prolong the QT interval within 14 days prior to the first dose of study treatment.

Sponsors & Collaborators

• Beijing Pearl Biotechnology Limited Liability Company: lead

Study Sites (2)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

NOT YET RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

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

• Yilong Wu, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weizhe Xue, Ph.D

CONTACT

+86-10-84148931; xueweizhe@pearlbio.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: April 16, 2025
• Study Start: July 7, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-01

Locations

CN (2)