Non-small-cell lung cancer
Conditions
Interventions
Cohort A (driver gene-negative):Vebreltinib combined with docetaxel
Cohort B (driver gene-positive):Vebreltinib combined with sacituzumab tirumotecan
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Ability to understand and voluntarily provide written informed consent. 2. Male or female, aged 18 to 75 years. 3. Patients with histologically or cytologically confirmed non-small cell lung cancer (NSCLC), clinically diagnosed as locally advanced (Stage IIIB/IIIC), metastatic, or recurrent (Stage IV) disease. 4. MET overexpression confirmed by IHC, defined as IHC 3+ in >= 50% of tumor cells. Tumor tissue from primary and/or metastatic sites and prior test results are acceptable. If archived tissue is negative for MET overexpression, a fresh biopsy sample must be submitted per investigator's discretion to reassess MET expression status. 5. Cohort A: Documented negative for known driver gene alterations (including but not limited to EGFR mutations, ALK fusions, ROS1 rearrangements, BRAF V600E mutations, NTRK fusions, MET exon 14 skipping mutations, RET rearrangements, HER2 mutations, KRAS activating mutations); and must have received at least one prior line of standard systemic therapy. 6. Cohort B: Presence of a known EGFR sensitizing mutation, and must have received >= 2 prior lines of standard therapy. 7. At least one measurable lesion as per RECIST version 1.1 criteria (previously irradiated lesions cannot be considered target lesions unless clear progression has been demonstrated post-radiation). 8. Eastern Cooperative Oncology Group (ECOG) performance status of = 1.5 × 10^9/L (without granulocyte colony-stimulating factor support within 7 days). (2) Hemoglobin (Hb) >= 90 g/L (without transfusion or growth factor support within 7 days). (3) Platelet count >= 75 × 10^9/L (without transfusion support within 7 days). (4) Total bilirubin = 60 mL/min, calculated using the Cockcroft-Gault formula: [(140 - age [years]) × weight (kg) × 1.23 (× 0.85 if female)] / serum creatinine (µmol/L). (7)International normalized ratio (INR) = 3 months, in the investigator's judgment.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with MET-targeting agents. 2. Cohort A only: Previous treatment regimen contained docetaxel. 3. Presence of spinal cord compression, leptomeningeal metastasis, or symptomatic brain metastases requiring escalating doses of steroids for CNS disease control. Note: Patients with controlled symptomatic CNS metastases are eligible, provided they have stable neurological status without new deficits on examination and no new CNS lesions on imaging. Steroid doses must have been stable for at least 2 weeks prior to study entry. 4. History of other active malignancies within the past 3 years, except for completely resected carcinoma in situ of any type, basal cell or squamous cell skin cancer, or other cancers treated with curative intent and without evidence of disease for at least 3 years. 5. Prior anti-cancer therapy meeting any of the following criteria: (1) Received anti-cancer or investigational drugs within 2 weeks or 5 half-lives (whichever is longer) before the first study dose. (2) Received Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 1 week before the first study dose. (3) Received radiotherapy to lung fields/whole brain within 4 weeks, or to other sites (excluding lung/whole brain) within 2 weeks, before the first study dose (except for palliative radiotherapy for bone metastases). (4) Underwent major surgery within 4 weeks (or brain metastasis resection within 2 weeks) before the first study dose, or has not recovered from surgical side effects. Thoracoscopic biopsy and mediastinoscopy are not considered major surgery; patients may enroll >= 1 week post-procedure. 6. Has not recovered from toxicities/complications of prior anti-cancer therapies (chemotherapy, surgery, radiotherapy) to Grade 160 mmHg and/or DBP >100 mmHg after treatment). Initiation or adjustment of antihypertensive therapy prior to screening is permitted. (2) Active infection requiring systemic anti-infective therapy within 2 weeks before the first study dose. (3) HIV-positive; HCV-Ab positive with detectable HCV-RNA; HBsAg positive with HBV-DNA >= 500 IU/mL (unless antiviral therapy reduces HBV-DNA to = 2 weeks before screening, with continued therapy during study). (4) Active tuberculosis. (5) Any condition deemed by the investigator to compromise patient safety or protocol compliance. 9. Cardiac function/disease meeting any of the following: (1) Mean QTcF interval > 470 ms on three ECGs at screening. (2) Clinically significant arrhythmias (e.g., uncontrolled ventricular, supraventricular, nodal arrhythmias; complete left bundle branch block, third-degree AV block, second-degree heart block, PR interval >250 ms). (3) Risk factors for QTc prolongation (e.g., severe hypokalemia, congenital long QT syndrome, concomitant QT-prolonging drugs). (4) Congestive heart failure >=NYHA Class III or LVEF < 50% on echocardiography. 10. History of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid treatment; current ILD or ongoing clinical intervention for active pul
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (Investigator); | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (DCR) by Investigator;Duration of response (DoR) by Investigator;Progression-free survival (PFS) by Investigator;Overall survival (OS) ;Safety; | — |
Countries
China
Contacts
Public ContactWang Yongsheng
West China Hospital of Sichuan University
Outcome results
None listed