Firmonertinib in Perioperative Treatment of Resectable Stage II-IIIB EGFR-mutated Lung Adenocarcinoma

Официальное название

An Open-label, Single-arm, Phase II Clinical Study of Firmonertinib in Perioperative Treatment of Resectable Stage II-IIIB EGFR-mutated Lung Adenocarcinoma

Обзор

An Open-label, Single-arm, Phase II Clinical Study of Firmonertinib in Perioperative Treatment of Resectable Stage II-IIIB EGFR-mutated Lung Adenocarcinoma

Вмешательства

• Препарат Firmonertinib 80mg qd oral for 8 weeks.
  Participations will receive the drug treatments preoperatively: Firmonertinib 80mg qd oral for 8 weeks. Radical tumor resection will be completed 3-4 weeks after the end of drug treatment.
• Препарат Firmonertinib 160mg qd oral for 8 weeks.
  Participations will receive the drug treatments preoperatively: Firmonertinib 160mg qd oral for 8 weeks. Radical tumor resection will be completed 3-4 weeks after the end of drug treatment.
• Препарат Firmonertinib 80mg qd oral for 16 weeks.
  Participations will receive the drug treatments preoperatively: Firmonertinib 80mg qd oral for 16 weeks. Radical tumor resection will be completed 3-4 weeks after the end of drug treatment.

Первичные конечные точки

• Major Pathological Response (MPR) Rate [Срок оценки: At the time of surgery (approximately Week 12 from treatment initiation for Cohort 1 and Cohort 2, and Week 20 for Cohort 3), Assessed up to 3 years]

Вторичные конечные точки (8)

• Objective Response Rate (ORR) [Срок оценки: From baseline up to the pre-operative tumor assessment (at Week 8 for Cohort 1 and Cohort 2, and at Week 16 for Cohort 3). Assessed up to 3 years]
• Disease Control Rate (DCR) [Срок оценки: From baseline up to the pre-operative tumor assessment (at Week 8 for Cohort 1 and Cohort 2, and at Week 16 for Cohort 3). Assessed up to 3 years]
• Pathological Complete Response (pCR) Rate [Срок оценки: From baseline up to the pre-operative tumor assessment (at Week 8 for Cohort 1 and Cohort 2, and at Week 16 for Cohort 3). Assessed up to 3 years]
• R0 Resection Rate [Срок оценки: At the time of surgery (approximately Week 12 from treatment initiation for Cohort 1 and Cohort 2, and Week 20 for Cohort 3) compared to baseline clinical staging. Assessed up to 3 years]
• Pathological Lymph Node Downstaging Rate [Срок оценки: From baseline up to the pre-operative tumor assessment (at Week 8 for Cohort 1 and Cohort 2, and at Week 16 for Cohort 3). Assessed up to 3 years]
• Disease-Free Survival (DFS) [Срок оценки: From the date of radical surgery up to the date of first documented disease recurrence or death from any cause, assessed up to 3.5 years]
• Incidence and Severity of Adverse Events (AEs) [Срок оценки: From the first dose of study drug until 28 days after the last dose of study drug, and throughout the perioperative/adjuvant treatment period assessed up to 3.5 years]
• Incidence of Surgical Complications [Срок оценки: Within 30 days following the surgical procedure assessed up to 3.5 years]

Критерии участия

Критерии включения

• 1.Prior to the initiation of any study-related procedures, including examinations, sample collection, or analyses, written informed consent was obtained from all participating patients.

2.Male or female, aged >=18 years; 3.Histologically or cytologically confirmed primary lung adenocarcinoma within 60 days prior to study entry.

4.Stage II-IIIB disease (AJCC 9th edition) confirmed by systematic imaging (contrast-enhanced chest/abdominal CT, brain CT/MRI, bone scan, or PET/CT), with lesions eligible for radical resection.

5.EGFR mutation-positive (19Del and/or L858R, with or without T790M) as determined by NGS testing of tumor tissue or blood.

6.At least one measurable lesion with a longest diameter >=10 mm on baseline CT scan (except lymph nodes, which must have a short-axis diameter >=15 mm), and suitable for accurate and repeated measurement.

7.ECOG performance status 0-1. 8. Female patients should take adequate and effective contraception, must not breastfeed, and have a negative pregnancy test before the first administration of the study drug; or female patients must meet the following criteria at screening to demonstrate infertility:

• Postmenopausal, defined as older than 50 years of age and having no menstruation for at least 12 months after stopping all exogenous hormone therapy.
• For women under 50 years old, if there is no menstruation for 12 months or longer after stopping exogenous hormone therapy, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are in the postmenopausal range, they are considered postmenopausal.
• Documented irreversible sterilization surgery, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, excluding tubal ligation.

9\. Male patients should be willing to use barrier contraception, i.e., condoms.

Критерии исключения

• 1.Tumors with squamous cell carcinoma, large cell carcinoma, or neuroendocrine components such as small cell carcinoma.

2.Presence of EGFR exon 20 insertion mutation detected by genetic testing. 3.Prior exposure to other antitumor therapies before enrollment. 4.Major surgery within 4 weeks prior to the first dose of study drug (including surgery for the primary tumor, excluding procedures for vascular access).

5.Scheduled or planned medical procedures (e.g., endoscopy or biopsy) or surgical operations within the next 4 months.

6.The patient is pregnant or breastfeeding. 7.Use of strong CYP3A4 inhibitors within 7 days, or strong CYP3A4 inducers within 21 days prior to the first dose of study drug; use of traditional Chinese medicines or herbal preparations indicated for antitumor treatment, those with tumor adjuvant effects, or any other agents with known antitumor activity within 14 days prior to the first dose.

8.History of other malignancies or concurrent malignancies, except for those that have been definitively treated with curative intent and with no evidence of recurrence for at least 5 years (e.g., carcinoma in situ of the cervix, basal cell carcinoma of the skin, or papillary thyroid carcinoma).

9.Patients with severe or uncontrolled systemic diseases requiring treatment, deemed unsuitable for participation by the investigator. These include but are not limited to: uncontrolled hypertension, diabetes, chronic heart failure (NYHA class III-IV), unstable angina, myocardial infarction within the past year, active bleeding disorders; hepatitis B (including all HBsAg-positive patients), hepatitis C (HCV antibody positive), or human immunodeficiency virus (HIV) infection; as well as patients with active infections requiring intravenous treatment.

10.Patients with severe gastrointestinal dysfunction or clinical conditions that may affect the intake, transport, or absorption of the study drug, such as inability to take oral medication, uncontrolled nausea and vomiting, or a history of extensive gastrointestinal resection.

11\. Meets any of the following cardiac assessment criteria: (1) Resting ECG corrected QT interval (QTc) >470 msec, with QTc corrected using the Fridericia formula (if the initial ECG shows QTc >470 ms, repeat the ECG twice and take the average of the three QTc results). (2) Any clinically significant abnormalities in heart rhythm, conduction, or morphology on resting ECG, such as complete left bundle branch block, second-degree or third-degree atrioventricular block, etc. (3) Any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, sudden unexplained death in first-degree relatives under 40 years old, or taking any concomitant medication known to prolong the QT interval that cannot be discontinued.

12\. History of interstitial lung disease (ILD), drug-induced interstitial lung disease, radiation pneumonitis requiring glucocorticoid treatment, or patients with clinical manifestations suspected to be interstitial lung disease.

13\. Any of the following laboratory test results indicating insufficient bone marrow or organ reserve function: (1) Absolute neutrophil count <1.5×10\^9/L; (2) Platelet count <100×10\^9/L; (3) Hemoglobin <90 g/L; (4) Alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN); (5) Aspartate aminotransferase (AST) >2.5×ULN; (6) Total bilirubin >1.5×ULN or, in the case of Gilbert's syndrome (unconjugated hyperbilirubinemia), >3×ULN; (7) Creatinine clearance <50 mL/min (calculated by the Cockcroft-Gault formula); (8) Prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) >=1.5 times ULN; 14. Known or suspected allergy to pralsetinib or any other component of its formulation; 15. Other situations where the patient is unable to comply with study procedures, restrictions, or requirements, and the investigator considers that such patient should not or is unsuitable to participate in the study; 16. Patients currently or previously participating in any other anti-tumor clinical study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07622706 · 2026YJZ05 · ChiCTR2600123002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• ChiCTR ChiCTR2600123002 (Китайский реестр КИ)

Открыть это исследование на ClinicalTrials.gov ↗