This study is a Phase III, international, multicenter, randomized, controlled, open-label clinical trial. The primary objective is to evaluate the efficacy and safety of furmonertinib plus platinum-based doublet chemotherapy (Arm A) versus osimertinib monotherapy (Arm B) in patients with EGFR sensitizing mutation-positive non-squamous non-small cell lung cancer (NSCLC) and brain metastases. Additionally, a proportion of subjects will receive furmonertinib monotherapy (Arm C) to further explore its efficacy and safety profile.
Stage 1 is the safety run-in phase, planned to enroll approximately 30 subjects who will be randomized at a 1:1 ratio to receive either furmonertinib 80 mg QD plus platinum-based chemotherapy or furmonertinib 160 mg QD plus platinum-based chemotherapy, aiming to evaluate the safety and tolerability of different furmonertinib doses in combination with platinum-based chemotherapy.
Stage 2 is the randomized controlled phase, in which approximately 350 subjects will be randomized in a 3:3:1 ratio (Arm A : Arm B : Arm C) to receive the investigational treatments.
Fully understand the trial and voluntarily sign the informed consent form;
Age ≥18 years at the time of signing ICF, regardless of gender;
Histologically/cytologically confirmed non-squamous NSCLC with brain parenchymal metastases assessed by BICR; Subjects with both brain parenchymal and leptomeningeal metastases are eligible. Subjects without brain metastases may be enrolled in the safety run-in phase.
For subjects with brain metastases: clinically stable for ≥4 weeks prior to first dose AND no requirement for corticosteroids/anticonvulsants for ≥14 days prior to first dose; Investigator-confirmed no need for local therapy for brain metastases during screening.
The tumor histology or cytology confirmed that the combination of neuroendocrine carcinoma, sarcomatoid carcinoma or squamous cell carcinoma was more than 10%;
Known subjects with ALK positive, ros1 positive, RET fusion positive, ntrk fusion positive, BRAF V600 mutation, met exon 14 skipping variant and other approved drugs for this target;
Subjects with meningeal metastasis but no brain parenchymal metastasis confirmed by MRI and / or CSF malignant cell examination;
Have received any systemic anti-tumor therapy targeting EGFR in the past, including those in clinical research stage (including EGFR TKI, monoclonal antibody, bispecific antibody, etc.);