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.
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)
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)
Second Affiliated Hospital of Nanchang University
Lead sponsor
Beijing Pearl Biotechnology Limited Liability Company
Collaborator