Phase Ib/II Study of Vebreltinib With Furmonertinib in NSCLC Patients With c-Met Amplification After EGFR-TKI Failure

NCT07087223 | Recruiting Phase 1 DMC

• 1 other identifier: 2024YJZ133
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 12

Brief Summary

The goal of phase Ib study was to evaluate efficacy and tolerability of the combination of vebreltinib and furmonertinib in patients with locally advanced or metastatic non-small cell lung cancer with c-met amplification after failure of EGFR-TKI treatment; to determine the maximum tolerated dose (MTD), and to evaluate the dose-limiting toxicity (DLT) and (recommended Phase 2 dose) RP2D of vebreltinib with furmonertinib. The goal of phase II study was to evaluate efficacy \[overall response rate (ORR), progression-free survival (PFS), and so on\] of vebreltinib and furmonertinib in patients with locally advanced or metastatic non-small cell lung cancer with c-met amplification after failure of EGFR-TKI treatment.

Conditions

Non Small Cell Lung Cancer NSCLC

Outcome Measures

Primary Outcomes (4)

• phase Ib: Incidence of dose-limiting toxicities (DLT) as defined in the protocol

  To determine the maximum tolerated dose (MTD) and/or dose-limiting toxicities (DLT) of combination therapy of Vebreltinib combined with Furmonertinib in locally advanced or metastatic NSCLC patients with c-Met amplification after EGFR-TKI failure

  12 months

• phase Ib: maximum tolerated dose (MTD)

  To determine the maximum tolerated dose (MTD) and/or dose-limiting toxicities (DLT) of combination therapy of Vebreltinib combined with Furmonertinib in locally advanced or metastatic NSCLC patients with c-Met amplification after EGFR-TKI failure

  12 months

• phase Ib: Recommended Phase II Dose (RP2D)

  To determine the recommended phase II dose (RP2D) of Vebreltinib in combination with Furmonertinib in locally advanced or metastatic NSCLC patients with c-Met amplification after EGFR-TKI failure

  12 months

• phase II: Overall Response Rate (ORR）

  ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1

  24 months

Secondary Outcomes (6)

• phase II: Progression Free Survival(PFS)

  24 months

• phase II: Duration of Response(DOR)

  24 months

• phase II: Disease Control Rate(DCR)

  24 months

• phase II: Overall Survival(OS)

  60 months

• phase II: adverse events

  Through study completion, an average of 2 year

Study Arms (3)

phase Ib Dose Escalation

EXPERIMENTAL

Drug: Vebreltinib combined with Furmonertinib

phase Ib Dose Expansion

EXPERIMENTAL

Drug: Vebreltinib combined with Furmonertinib

phase II

EXPERIMENTAL

Drug: Vebreltinib combined with Furmonertinib

Interventions

Vebreltinib combined with Furmonertinib DRUG

Vebreltinib 100mg/1500mg/200mg oral twice daily combined with Furmonertinib 80mg oral once daily

phase Ib Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Fully aware this study and voluntary to sign the informed consent form, and willing and able to comply with the study procedure.
• Aged ≥18 years, male or female.
• Patients with histologically or cytologically confirmed unresectable and non-suitable for radical surgery, or concurrent chemoradiotherapy , locally advanced or metastatic (stage IIIB, IIIC or IV) NSCLC;
• Documented EGFR sensitive mutations (exon 19 deletion or exon 21 L858R mutation).
• Disease progression after prior EGFR-TKI therapy. Participants must meet both of the following 2 criteria:
• (1) ≤1 prior chemotherapy regimen allowed besides EGFR-TKI. Combination with anti-angiogenic therapy or PD-1/PD-L1 inhibitors are allowed during EGFR-TKI targeted therapy or chemotherapy.
• （2） Objective clinical benefit documented during previous EGFR-TKI therapy, defined by either partial or complete radiological response, or durable stable disease should be greater than 6 months after initiation of EGFR-TKI.
• \. After the last line of treatment before enrollment, progression is confirmed, and blood tests confirm c-Met amplification, or re-biopsy and genetic testing confirm c-Met amplification. Any of the following criteria define c-Met amplification.
• For tumor tissue samples, FISH detection shows GCN ≥5 and/or MET/CEP7 ≥2 (FISH results from local testing institutions/central laboratories are acceptable);
• Tissue (wax blocks from pleural effusion centrifugation, if quality-controlled) or blood NGS testing results confirm c-Met amplification with CN ≥2.3 (NGS results from local testing institutions/central laboratories are acceptable for both tissue and blood).
• \. ECOG performance status ≤1. 8. According to RECIST v1.1, the patient must have at least one target lesion as assessed by the investigator.
• \. Laboratory test results must meet the following criteria:
• Absolute neutrophil count ≥1.5×10⁹/L (without the use of growth factors within 7 days prior to the start of treatment);
• Hemoglobin ≥90 g/L (without blood transfusion or use of growth factors within 7 days prior to the start of treatment);
• Platelet count ≥75×10⁹/L (without blood transfusion or use of growth factors within 7 days prior to the start of treatment);

You may not qualify if:

• Patients with ALK fusion or ROS1 fusion.
• Patients with spinal cord compression, leptomeningeal metastasis, or symptomatic brain metastasis that requires an increase in steroid dosage to control central nervous system disease. Patients with symptomatic CNS metastases that have been controlled may be eligible for this trial.
• Presence of other malignancies (with the exception of any type of carcinoma in situ that has been completely resected, basal cell and squamous cell skin cancers, or other tumors/cancers that have been treated with curative intent and have been disease-free for at least 3 years).
• A history of anti-tumor treatment that meets any of the following criteria:
• （1）Received traditional Chinese medicine or patent medicine with anti-tumor indications within 1 week prior to the first dose of the study drug; （2）Underwent radiotherapy targeting the lung fields and whole brain within 4 weeks prior to the first dose of the study drug, or received radiotherapy targeting other areas (excluding the lung fields and whole brain) within 2 weeks prior to the first dose. Palliative radiotherapy for bone metastases to relieve pain or prevent skeletal-related events is excluded; （3）Underwent major surgery within 4 weeks, or has not recovered from the adverse effects of these surgeries. Thoracoscopic biopsy and mediastinoscopy are not considered major surgeries, and patients may be enrolled ≥1 week after the procedure 5. Has not recovered from any toxicity or complications of prior chemotherapy, surgery, radiotherapy, or other anti-tumor treatments, i.e., not reduced to ≤Grade 1 (NCI-CTCAE v5.0), with the exception of alopecia and permanent radiation-induced damage that cannot be recovered; 6. Requires the use of strong inhibitors or inducers of cytochrome P450 3A4 enzyme 1 week prior to the first dose of the study drug and during the study period.
• \. Has any severe or uncontrolled systemic disease, including but not limited to:
• Uncontrolled hypertension, with the allowance for the initiation or adjustment of antihypertensive medications prior to screening;
• Positive for anti-HIV, or positive for both anti-HCV and HCV-RNA, or positive for HBsAg with HBV-DNA ≥500 IU/mL
• Active keratitis or ulcerative keratitis during the disease phase;
• Active tuberculosis;
• Active infection requiring systemic antimicrobial therapy within 2 weeks prior to the first dose of the study drug;
• Other severe medical conditions or psychiatric disorders, or laboratory abnormalities that, in the investigator's judgment, make the study drug unsuitable for the patient or affect protocol compliance; 8. Cardiac dysfunction and diseases that meet any of the following criteria:

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (12)

Ordos Central Hospital

Neimeng, Neimeng, China

NOT YET RECRUITING

Peking University Cancer Hospital (Inner Mongolia Campus)

Neimeng, Neimeng, China

NOT YET RECRUITING

Affiliated Hospital of Hebei University

Baoding, China

NOT YET RECRUITING

Baotou Cancer Hospital

Baotou, China

RECRUITING

Peking University Cancer Hospital & Institute

Beijing, 100142, China

RECRUITING

Beijing Chest Hospital, Capital Medical University

Beijing, China

NOT YET RECRUITING

Beijing Daxing District People's Hospital

Beijing, China

NOT YET RECRUITING

Peking Union Medical College Hospital

Beijing, China

NOT YET RECRUITING

Peking University People's Hospital

Beijing, China

NOT YET RECRUITING

Peking University Third Hospital

Beijing, China

NOT YET RECRUITING

The Second Hospital of Dalian Medical University

Dalian, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

NOT YET RECRUITING

MeSH Terms

Interventions

aflutinib

Central Study Contacts

Minglei Zhuo

CONTACT

+86 88196456; minglei1978@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 25, 2025
• Study Start: April 8, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)