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.);
Parallel
Furmonertinib Mesilate Tablets
DrugUsage and dosage: 80mg, 240mg, or 160mg QD orally Medication duration: A cycle of 21 days until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs
Carboplatin Injection
DrugUsage and dosage: Administer via IV infusion, with a dosage of AUC5, not exceeding 750 mg. Medication schedule: every 3 weeks as a cycle, D1 administration per cycle, immediate administration of carboplatin upon completion of pemetrexed infusion, intravenous infusion, carboplatin can be used for up to 4 cycles.
Cisplatin for injection
DrugUsage and dosage: Administer via IV infusion at a dose of 75 mg/m2. Medication schedule: Every 3 weeks as a cycle, with D1 administration per cycle. Cisplatin is administered approximately 30 minutes after the infusion of pemetrexed, via intravenous infusion. Adequate hydration therapy must be received before and after cisplatin treatment. Cisplatin can be used for up to 4 cycles.
Pemetrexed Disodium for Injection
DrugUsage and dosage: Intravenous (IV) infusion administration, dosage of 500 mg/m2 Medication schedule: Administer on the first day of each cycle (21 days per cycle, i.e. every 3 weeks) until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs.
Osimertinib Mesylate Tablets
DrugUsage and dosage: 80mg, QD administration Medication duration: A cycle of 21 days until intolerable toxicity, disease progression, death, or initiation of new anti-tumor therapy occurs
Adverse Events (AE)
Safe import period
Serious Adverse Event (SAE)
Safe import period
Progression-free survival (PFS)
Randomized Controlled Phase：PFS assessed by BICR based on recist1.1; PFS was defined as the time from the date of randomization to the date of first documented disease progression (assessed according to RECIST v1.1 criteria) or death from any cause, whichever occurred first.
Progression free survival (PFS) evaluated by researchers based on RECIST 1.1
Both the safe introduction period and randomized controlled trials require evaluation of progression free survival (PFS)
Objective response rate (ORR)
Both the safe introduction period and randomized controlled trials require evaluation of objective response rate (ORR)
Disease control rate (DCR)
Both the safe introduction period and randomized controlled trials require evaluation of disease control rate (DCR)
Duration of Relief (DOR)
Both the safe introduction period and randomized controlled trials require evaluation of Duration of Relief (DOR)
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