A Single-Arm, Multicenter, Phase II Clinical Trial of Firmonertinib in Combination With Definitive Radiotherapy for Patients With Stage III Unresectable Pulmonary Adenocarcinoma Harboring Positive EGFR Uncommon Driver Mutations
This is a prospective, single-arm, Phase II clinical study aimed at evaluating the efficacy and safety of 160mg fimonertinib in combination with definitive radiotherapy for patients with EGFR uncommon driver mutation-positive, Stage III unresectable lung adenocarcinoma. The primary endpoint is Progression-Free Survival (PFS), assessed by the investigator according to RECIST 1.1 criteria, defined as the time from the first dose to objective disease progression or death (from any cause). Secondary endpoints include PFS by different mutation types, OS, ORR, DCR, as well as adverse events and their severity.
• Provision of informed consent prior to any study-specific procedures;
• Age ≥18years;
• ECOG performance status of 0 or 1 with no deterioration within the 2 weeks prior to enrollment, and a life expectancy of ≥12 weeks;
• Histologically or cytologically confirmed non-squamous non-small cell lung cancer;
• Assessed as having unresectable or inoperable locally advanced non-squamous non-small cell lung cancer suitable for definitive radiotherapy (Stage III according to AJCC 9th edition TNM staging);
• Presence of EGFR uncommon mutations (excluding 19del, L858R, T790M) confirmed by genetic testing in a tertiary grade A hospital; specific types are detailed in Appendix 11;
• No prior systemic anti-tumor therapy or radiotherapy for locally advanced non-small cell lung cancer before the first dose of the study drug, including chemotherapy, biologic therapy, targeted therapy, immunotherapy, or investigational drug therapy;
• At least one accurately measurable lesion according to RECIST 1.1, which has not been previously irradiated and was not biopsied during the screening period. If a subject has only one measurable lesion, biopsy of that lesion is permitted, provided the baseline imaging is performed at least 14 days after the biopsy;
• Female subjects must use highly effective contraception (see restrictions) for at least 2 weeks prior to the first dose, have a negative pregnancy test, must not be breastfeeding at the time of treatment initiation, OR must meet at least one of the following criteria at screening to demonstrate the absence of childbearing potential;
‣ Postmenopausal, defined as age over 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormonal treatments;
⁃ For women aged 50 years or younger, amenorrhea for 12 months or more after cessation of exogenous hormone therapy and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the institutional postmenopausal range;
⁃ Irreversible surgical sterilization documented by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but excluding tubal ligation;
⁃ Male subjects must be willing to use barrier contraception ;
⁃ Ability to comply with the study protocol and follow-up procedures, and capable of oral medication intake