Clinical trial NCT06644313: Vebreltinib for Neoadjuvant in MET-altered Stage IIIA-IIIB (N2) Non-small Cell Lung Cancer (NSCLC)
Official title: Vebreltinib for Neoadjuvant in MET-altered Stage IIIA-IIIB (N2) Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Potentially Resectable MET-altered Non-Small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer Stage III
Non-small Cell Lung Cancer with MET mutation
Neoadjuvant
Vebreltinib
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2024-10-16
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All enrolled patients received Vebreltinib neoadjuvant therapy.
Primary purpose: TREATMENT

Brief summary: According to the 2024 edition of the NCCN guidelines and the 2023 edition of the CSCO guidelines, perioperative treatment is recommended for patients with stage IIIA and IIIB (T3N2) non-small cell lung cancer (NSCLC). Targeted therapies for NSCLC, such as EGFR inhibitors and ALK inhibitors, have been explored in the neoadjuvant setting. For patients with MET alterations, some have undergone preoperative MET inhibitor treatment, achieving pathological downstaging followed by surgery, resulting in R0 resection. Therefore, this is a prospective, cohort, single-center phase II clinical study to evaluate the efficacy and safety of Vebreltinib as a neoadjuvant treatment for patients with MET-altered stage IIIA-IIIB (N2) NSCLC.


Eligibility criteria: Inclusion Criteria:

* 1. The patient shall sign the Informed Consent Form. 2.Aged 18 ≥ years. 3.Histological or cytological diagnosis of NSCLC by needle biopsy, and evaluated by researchers as stage III-IVA.

  4.NGS gene testing confirmed MET alterations, which include the following two types: Cohort 1: MET exon 14 skipping mutations (NGS results from tissue or blood samples certified by CLIA or CAP-approved laboratories); Cohort 2: Primary MET amplification (NGS results or FISH results from tissue or blood samples certified by CLIA or CAP-approved laboratories)..

  5.Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. 6. According to the MDT evaluation (which should include a thoracic surgeon specializing in tumor surgery), it is considered that the primary NSCLC is potentially completely resectable; 7. At least 1 measurable lesion according to RECIST 1.1. 8.Patients with good function of other main organs (liver, kidney, blood system, etc.) 9.Patients with lung function can tolerate surgery; 10.Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative. 11. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 d

Exclusion Criteria:

* 1. Previously received targeted therapy (including TKI or monoclonal antibodies), immunotherapy, or any investigational drug treatment for NSCLC; 2.Pathological confirmation of mixed small cell and non-small cell lung cancer; 3.Patients with a malignancy other than NSCLC within five years prior to the start of this trial，except for cured basal cell carcinoma of the skin, early gastrointestinal (GI) carcinoma excised through endoscopy, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, or any cured cancer deemed to have no impact on the survival of the current NSCLC; 4.Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\&gt;= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases; 5.Patients with congenital or acquired immune dysfunction (such as HIV infected individuals); 6.Received other major surgical treatments (excluding diagnosis) within 4 weeks prior to the start of the study or expected to undergo major surgical treatments during the study period; 7.Participants who are allergic to the test drug or any auxiliary materials; 8.A history of extensive diffuse bilateral interstitial fibrosis in the past or before medication, or a known grade 3 or 4 history of interstitial fibrosis or interstitial lung disease, including pneumonia, allergic pneumonia, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not including local radiation pneumonia or radiation pulmonary fibrosis history;8. Pregnant or lactating women; 9.Any malabsorption; 10.Participants suffering from nervous system diseases or mental diseases that cannot cooperate 11.Other factors that researchers think it is not suitable for enrollment.

Primary outcomes:
measure: Objective response (ORR) rate
timeFrame: up to 30 months
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: up to 30 months
measure: Major pathologic response (MPR) rate
timeFrame: Up to 30 months
measure: Pathologic complete response (PCR) rate
timeFrame: Up to 30 months
measure: Event-free survival (EFS)
timeFrame: up to 60 months
measure: 3-year overall survival (OS)
timeFrame: Up to 36 months
measure: Overall survival (OS)
timeFrame: up to 60 months
measure: Treatment-related adverse event (TRAE)
timeFrame: Up to 30 months
Other outcomes:
measure: The correlation between stratification factors such as disease stage, smoking history, and treatment efficacy
timeFrame: Up to 30 months
Locations:
Study officials:
References: