A Phase III, Randomized, Multicentre, Open Label Study to Assess the Efficacy and Safety of Firmonertinib Versus Platinum Based Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients With EGFR PACC Mutation or EGFR l861q Mutation
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Progression-free survival (PFS) assessed by the Independent Review Committee (BICR) according to RECIST v1.1.
研究概览
简要总结
This study is a randomized, open, multicenter phase III clinical study, which aims to evaluate the efficacy and safety of firmonertinib mesylate compared with platinum based chemotherapy for patients with locally advanced or metastatic NSCLC who have not been treated with systemic antitumor therapy and carry EGFR PaCC mutation or EGFR l861q mutation.
Eligible patients were stratified by EGFR mutation type and CNS metastasis at the time of enrollment. Approximately 300 patients would be randomly assigned 1:1 to receive either firmonertinib mesylate (240mg, orally on an empty stomach daily) or platinum containing dual agent chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form (ICF).
- •Age ≥18 years at the time of ICF signing.
- •At least one measurable lesion per RECIST v1.1, meeting the following:
- •No prior local therapy (e.g., radiotherapy)
- •Not used for biopsy during screening
- •Histologically/cytologically confirmed non-squamous NSCLC, classified as:
- •Locally advanced (Stage IIIB/IIIC, unsuitable for curative surgery and/or definitive chemoradiotherapy)
- •Metastatic (Stage IV) (Based on UICC/AJCC 8th edition TNM staging)
- •Agreement to provide:
- •Recent tumor tissue (from untreated lesions)
- •Blood samples
- •Central lab-confirmed EGFR PACC or L861Q mutation (If tumor tissue is unavailable due to inaccessible lesions, sponsor consultation is required.)
- •No prior systemic therapy for advanced/metastatic NSCLC.
- •Allowed if: Prior (neo)adjuvant/definitive chemoradiotherapy completed ≥12 months before recurrence/progression
- •ECOG performance status 0-
- •Life expectancy ≥12 weeks.
- •Adequate bone marrow/organ function within 14 days before treatment (no transfusion/G-CSF within 2 weeks prior).
- •Women of childbearing potential (WOCBP):
- •Abstinence or contraception use
- •No egg donation
- •Non-sterilized males:
- •Abstinence or contraception use
- •No sperm donation
- •CNS metastases allowed if protocol-specified criteria are met.
排除标准
- •Histologically/cytologically confirmed tumor with >10% neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell components.
- •Known ALK-positive, ROS1-positive, RET fusion-positive, NTRK fusion-positive, BRAF V600E mutation, MET exon 14 skipping mutation, or other targetable alterations with approved therapies.
- •Prior treatments including:
- •Systemic anti-tumor therapy for advanced/metastatic NSCLC (e.g., chemotherapy/targeted/immunotherapy). Neoadjuvant/adjuvant therapy exceptions per Inclusion Criterion #
- •>30 Gy thoracic radiotherapy within 6 months or non-thoracic radiotherapy within 4 weeks prior to first dose (brain radiotherapy exceptions per Inclusion Criterion #12).
- •Any prior EGFR-targeted therapy (including investigational EGFR-TKIs, mAbs, bispecific antibodies, etc.).
- •Strong CYP3A4 inhibitors within 7 days or inducers within 21 days prior to first dose.
- •Anticancer traditional Chinese medicines within 2 weeks prior to first dose.
- •Non-specific immunomodulators (e.g., interferon, IL-2, thymosin) within 2 weeks prior to first dose.
- •Major trauma/surgery within 4 weeks prior to treatment initiation.
- •Clinically significant gastrointestinal abnormalities, including:
- •Moderate/severe atrophic gastritis
- •GI obstruction/perforation
- •Chronic diarrhea/short bowel syndrome
- •Major upper GI surgery (e.g., gastrectomy)
- •Inflammatory bowel disease (Crohn's/ulcerative colitis) or active intestinal inflammation
- •Inability to swallow tablets
- •Uncontrolled systemic diseases.
- •Severe acute/chronic infections.
- •Interstitial lung disease (ILD)/non-infectious pneumonia:
- •History requiring clinical intervention
- •Current presence
- •Suspicious imaging findings unresolved at screening
- •Clinically significant cardiovascular dysfunction (active or history).
- •Tumor invasion of critical adjacent structures (heart/esophagus/SVC etc.) with high bleeding/fistula risk. Exceptions may be considered if investigator assesses minimal risk.
- •Pulmonary comorbidities causing severe impairment, including:
- •Baseline lung diseases (e.g., pulmonary embolism [≤3 months], severe asthma/COPD/restrictive disease)
- •Autoimmune/connective tissue disorders with pulmonary involvement (e.g., rheumatoid arthritis, sarcoidosis)
- •Residual toxicity >Grade 1 (per NCI CTCAE v5.0) from prior anticancer therapy (except alopecia/neuropathy).
- •Concurrent malignancies except:
- •Cured localized skin cancers (BCC/SCC), superficial bladder cancer, cervical/breast DCIS, or papillary thyroid cancer
- •Other malignancies cured by radical therapy ≥3 years prior
- •Pregnancy/lactation or planned pregnancy within 6 months post-treatment.
- •Inability to comply with study procedures/follow-up.
- •Known hypersensitivity to furmonertinib or excipients.
- •History of allergic reactions to pemetrexed/cisplatin/carboplatin.
- •Other exclusionary per investigator judgment, including:
- •Alcohol/drug abuse
- •Severe comorbidities (including psychiatric) requiring treatment
- •Critical laboratory abnormalities
- •Social/familial factors compromising safety/data collection
研究组 & 干预措施
Firmonertinib
Oral administration, 240mg, QD。
干预措施: Firmonertinib Mesilate Tablets (Drug)
chemotherapy
Pemetrexed Disodium for Injection： 500mg/m2, intravenous infusion. Cisplatin for injection：75 mg/m2， intravenous infusion. Carboplatin Injection：administered according to the AUC of 5 mg/ml, intravenous infusion.
干预措施: Carboplatin Injection (Drug)
chemotherapy
Pemetrexed Disodium for Injection： 500mg/m2, intravenous infusion. Cisplatin for injection：75 mg/m2， intravenous infusion. Carboplatin Injection：administered according to the AUC of 5 mg/ml, intravenous infusion.
干预措施: Cisplatin for injection (Drug)
chemotherapy
Pemetrexed Disodium for Injection： 500mg/m2, intravenous infusion. Cisplatin for injection：75 mg/m2， intravenous infusion. Carboplatin Injection：administered according to the AUC of 5 mg/ml, intravenous infusion.
干预措施: Pemetrexed Disodium for Injection (Drug)
结局指标
主要结局
Progression-free survival (PFS) assessed by the Independent Review Committee (BICR) according to RECIST v1.1.
时间窗: Up to 3 years
The time from the date of randomization to the date of first documentation of disease progression (assessed according to RECIST v1.1 criteria) or death from any cause, whichever occurred first.
次要结局
- Overall survival (OS)(Up to 3 years)
- The incidence and severity of adverse events (AES) were determined according to NCI CTCAE V5.0(Up to 3 years)
- Patient Reported Outcomes by EORTC QLQ LC13 questionnaire(Up to 3 years)
- Patient Reported Outcomes by EORTC QLQ-C30 questionnaire(Up to 3 years)
- Plasma concentrations of firmonertinib and its major metabolite (ast5902) in patients treated with firmonertinib at the indicated sampling time points(Up to 3 years)