High-Dose Firmonertinib Plus Bevacizumab as Neoadjuvant Therapy for Resectable EGFRm Stage II-IIIB NSCLC

Официальное название

High-dose Firmonertinib Combined With Bevacizumab as Neoadjuvant Therapy in Stage II-IIIB, Resectable, EGFR-mutated Non-small Cell Lung Cancer Patients: A Single-arm, Multi-center, Open-label Phase II Clinical Study

Обзор

This is a Phase II, single-arm, open-label, multicenter clinical study aimed at evaluating the efficacy and safety of Firmonertinib 160 mg combined with Bevacizumab as neoadjuvant therapy in patients with resectable stage II-IIIB Epidermal Growth Factor Receptor(EGFR)-mutated non-small cell lung cancer.

Вмешательства

• Препарат Firmonertinib Mesilate Tablets
  Firmonertinib Mesilate Oral administration 160 mg once daily for 3 months before surgery. Radical tumor resection will be performed at least 6 weeks after completion of Bevacizumab treatment. After surgery, the treatment plan was determined by the researchers, with options including Firmonertinib Mesilate Tablets: Oral administration once daily, 80mg per dose, for 3 years or until disease progression or intolerable toxicity occurs.
• Препарат Bevacizumab injection
  Bevacizumab injection (intravenous infusion, 7.5 mg/kg) administered every 21 days as one cycle, for a total of 2 cycles. Radical tumor resection will be performed at least 6 weeks after completion of Bevacizumab treatment.

Первичные конечные точки

• pathological Complete Response(pCR) rate [Срок оценки: Within 24 hours after surgical resection]

Вторичные конечные точки (9)

• Major pathological response (MPR) rate [Срок оценки: Within 7 days after surgical resection]
• Radical resection rate [Срок оценки: Within 7 days after surgical resection]
• Lymph node downstaging rate [Срок оценки: Within 7 days after completion of neoadjuvant therapy and within 7 days after surgical resection]
• Pathological positive lymph node conversion rate [Срок оценки: Within 7 days after completion of neoadjuvant therapy and within 7 days after surgical resection]
• Objective response rate (ORR) by investigator [Срок оценки: Approximately 9 weeks following the first dose of Firmonertinib]
• Event-free survival (EFS) [Срок оценки: From first dose until the event of interest, assessed up to 36 months after the first dose]
• Safety: Occurrence and frequency of adverse events, severity, surgical complications [Срок оценки: From randomization to 30 days after treatment completion]
• Patient-reported outcomes: Change from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30) [Срок оценки: Day1/21/42/63/84 of Neoadjuvant Therapy]
• Patient-reported outcomes: Change from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13(QLQ-LC13) [Срок оценки: Day1/21/42/63/84 of Neoadjuvant Therapy]

Критерии участия

Критерии включения

• Male or female, aged ≥18 years.
• Histologically/cytologically confirmed primary non-small cell lung cancer within 60 days prior to the study.
• Stage II-IIIB disease evaluated by endobronchial ultrasound guided tranbronchial needle aspiration(EBUS-TBNA), mediastinoscopy, or Positron Emission Tomography/Computed Tomography (PET/CT), with lesions planned for radical resection after neoadjuvant therapy.
• EGFR mutation-positive confirmed by local laboratory testing of tissue or blood samples.
• Presence of at least one measurable lesion, with a baseline Computed Tomography (CT) scan showing the longest diameter ≥10 mm (except for lymph nodes, which must have a short axis ≥15 mm), and suitable for accurate repeated measurements.
• ECOG performance status score of 0-1, with no deterioration within 2 weeks prior to the first dose administration.
• Female patients should adopt fully effective contraceptive measures, must not be breastfeeding, 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 confirm the absence of reproductive potential:
• Postmenopausal, defined as age greater than 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormonal therapies.
• For women under 50 years of age, they are considered postmenopausal if they have not had a menstrual period for 12 months or more after stopping exogenous hormone therapy, and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the postmenopausal range.
• Documented irreversible sterilization procedures, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, excluding tubal ligation.
• Male patients should be willing to use barrier contraception, i.e., condoms.

Критерии исключения

• Presence of small cell lung cancer or mixed pathological types of NSCLC. EGFR exon 20 insertion mutation detected by genetic testing.
• Exposure to any other antitumor therapy prior to enrollment, including perioperative radiotherapy.
• The patient is in pregnancy or lactation.
• History of other malignant tumors, or currently combined with other malignant tumors (except for malignancies that have undergone radical surgery with no recurrence within 5 years post-operation, such as cervical carcinoma in situ, basal cell carcinoma of the skin, and papillary thyroid carcinoma, etc.).
• Presence of severe or uncontrolled systemic diseases requiring treatment, which the investigator deems unsuitable for trial participation, including hypertension, diabetes mellitus, chronic heart failure (New York Heart Association, NYHA Class III-IV), unstable angina, myocardial infarction within the past year, etc.
• Severe gastrointestinal dysfunction, diseases, or clinical conditions that may affect the intake, transport, or absorption of the study drug, such as inability to take oral medications, uncontrollable nausea and vomiting, extensive gastrointestinal resection history, etc.
• Any of the following laboratory tests indicate insufficient bone marrow reserve or organ reserve function.

• Absolute neutrophil count <1.5×10\^9/L
• Platelet count <100×10\^9/L
• Hemoglobin <90 g/L
• Alanine aminotransferase (ALT) >2.5×upper limit of normal (ULN)
• Aspartate aminotransferase (AST) >2.5×ULN
• Total bilirubin >1.5×ULN or >3×ULN in cases of Gilbert's syndrome (unconjugated hyperbilirubinemia)
• Known or suspected allergy to almonertinib mesylate, bevacizumab, or any other component of their formulations, or patients with other contraindications.
• If the patient cannot comply with the study procedures, restrictions, and requirements, or if the investigator deems the patient ineligible or unsuitable for participation in the study for any other reason.
• Patients currently or previously enrolled in any other anti-tumor clinical studies.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Cancer Hospital — Пекин

Идентификаторы

NCT: NCT07182708 · LGH2025343

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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