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Furmonertinib

Dongqing Lyu, MD

The investigators were to explore whether high-dose Furmonertinib, compared with osimertinib, could achieve longer survival in patients with EGFR-mutated NSCLC with CNS metastasis.

Lung cancer is the leading cause of cancer incidence and death worldwide. Non-small cell lung cancer accounts for about 80-85%, and EGFR mutations occur in about 45-55% of the Asian population. In newly diagnosed NSCLC patients, the rate of brain metastases in advanced NSCLC can be as high as 25% to 44%. The brain metastasis rate of advanced lung adenocarcinoma with EGFR mutation can reach 60%. For NSCLC patients with CNS metastases and EGFR mutations, the PFS of EGFR-TKIs was improved compared with chemotherapy, but neither was satisfactory, even with Osimertinib (third-generation EGFR-TKI). The PFS of patients with CNS metastases treated with Osimertinib was only 15.23 months. Therefore, the diagnosis and treatment of lung cancer patients with brain metastases is still a difficult problem to improve the long-term survival rate of lung cancer. Clinical data and early preclinical studies have shown that Furmonertinib(AST2818) can effectively inhibit the classical mutation of EGFR, especially for intracranial lesions, and is well tolerated. In the FURLONG study, the PFS of patients with CNS metastases was 20.8 months and the ORR were 91%, respectively. This may be due to the unique molecular structure of Furmonertinib, which has the advantage of "double entry into the brain". Furthermore, the investigators' previous research showed that patients treated with 160mg of Furmonertinib after third-generation EGFR-TKIs treatment resistance were divided into intracranial progression mode group and extracranial progression mode group, and finally proven that Furmonertinib 160mg with or without antiangiogenic agents could be an option for patients with advanced NSCLC who have developed resistance after third-generation EGFR-TKIs, especially those who have developed resistance due to intracranial lesion progression. Based on above, the investigators propose to develop a multi-center, randomized, controlled, prospective, Phase II clinical trial in order to explore whether high-dose Furmonertinib could achieve longer survival in patients with EGFR-mutated NSCLC with CNS metastasis, particularly long-term control of intracranial lesions.

High-dose Furmonertinib Versus Osimertinib in Advanced EGFRm NSCLC Patients With Brain Metastases

High-dose Furmonertinib Versus Osimertinib as First-line Treatment in Advanced EGFR Mutation-positive NSCLC Patients With Brain Metastases: a Multi-center, Randomized, Controlled, Prospective, Phase II Clinical Trial

The dynamic changes of ct-DNA in patients' blood before and after 3 weeks of medication

The time from the start of randomization until the first occurrence of disease. progression or death from any cause, whichever occurs first.

The proportion of patients with a complete or partial response

The proportion of patients with a complete or partial response of intracranial tumors

The time from the beginning of randomization to the first occurrence of objective progression or death of intracranial tumors, whichever occurs first.

The time from randomization to death from any cause

the proportion of patients with a complete response, partial response, or stable disease

the proportion of patients with a complete response, partial response, or stable disease(≥6w) of intracranial tumors

best percentage change in the sum of the longest diameter of target lesions compared with baseline in patients without progression of non-target lesions and the occurrence of new lesions

best percentage change in the sum of the longest diameter of target lesions in CNS compared with baseline in patients without progression of non-target lesions and the occurrence of new lesions

The time from randomization to the first assessment of CR or PR for intracranial tumor.

The time from the date of first documented response to the date of disease progression or death, whichever occurred first.

The time from the date of first documented response in CNS to the date of disease progression or death, whichever occurred first.

Changes in Karnofsky scores and neuro-oncology Scale scores from baseline

Changes in FACT-L scale scores from baseline

The type, frequency, severity, and degree of treatment-related adverse events (according to CTCAE version 5.0)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
High-dose Furmonertinib Versus Osimertinib in Advanced EGFRm NSCLC Patients With Brain Metastases	NCT06319950	Lung Cancer, No...	Furmonertinib Osimertinib	18 Years - 80 Years	Taizhou Hospital
High-dose Furmonertinib Versus Osimertinib in Advanced EGFRm NSCLC Patients With Brain Metastases	NCT06319950	Lung Cancer, No...	Furmonertinib Osimertinib	18 Years - 80 Years	Taizhou Hospital

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