Bozitinib Combined With Chemotherapy as Radical Treatment for Stage IIA-IIIC MET-Altered Non-Small Cell Lung Cancer

Обзор

This study aim to evaluate the efficacy and safety of Bozitinib combined with chemotherapy as radical treatment for stage IIA-IIIC MET-altered non-small cell lung cancer

Вмешательства

• Препарат Bozitinib
  Participants will receive bozitinib in combination with standard platinum-based doublet chemotherapy for 8 weeks. Following investigator-assessed operability, surgical resection will be performed approximately 4 weeks after completion of neoadjuvant therapy. The first MRD assessment will be conducted after completion of neoadjuvant therapy and before surgery.A second MRD assessment will be performed within 7 days to 1 month after surgery. Based on a comprehensive evaluation of MRD status, tumor

Первичные конечные точки

• Major Pathological Response [Срок оценки: Up to 6 month]

Вторичные конечные точки (6)

• Objective Response Rate [Срок оценки: Up to 6 month]
• Pathological Complete Response rate [Срок оценки: Up to 6 month]
• Disease Control Rate [Срок оценки: Up to 2 year]
• Event-Free Survival [Срок оценки: Up to 2 year]
• 3-Year Overall Survival [Срок оценки: Up to 3 year]
• Overall Survival [Срок оценки: Up to 5 year]

Критерии участия

Критерии включения

• Patients must meet all of the following inclusion criteria to participate in this study:
• Signed informed consent.
• Age ≥ 18 years.
• Histologically or cytologically confirmed NSCLC adenocarcinoma, with -postoperative pathology confirming stage IIA-IIIC.
• Willing to undergo curative resection, and assessed by a surgeon as operable with no surgical contraindications.
• No prior systemic anti-tumor therapy.
• Expected survival ≥ 6 months.
• At least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.
• MET alteration confirmed by NGS gene testing, including the following types:

MET exon 14 skipping mutation (NGS results from tissue or blood sample certified by CLIA or CAP).

• MET primary amplification, NGS positive or FISH GCN ≥6 (results from tissue or blood sample certified by CLIA or CAP or FISH assay).
• MET protein overexpression, immunohistochemistry showing ≥50% tumor cells with ++ or higher staining.
• Adequate pulmonary function to tolerate surgery.
• Adequate organ and bone marrow function, defined as:
• Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9.0 g/dL.
• Hepatic function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with HCC, liver metastases, or history/suspected Gilbert syndrome (persistent or recurrent hyperbilirubinemia, mainly unconjugated, without evidence of hemolysis or liver lesions), TBIL ≤ 3 × ULN; for patients without HCC or liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
• Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min; urine dipstick protein < 2+.
• Coagulation: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN.

Thyroid function: normal thyroid-stimulating hormone (TSH); if baseline TSH is outside the normal range, enrollment is allowed if total T3 (or FT3) and FT4 are within normal limits.

• Cardiac enzymes: within normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator are acceptable).
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study drug (Cycle 1, Day 1). If urine pregnancy test cannot be confirmed negative, a serum pregnancy test is required. Non-childbearing females are defined as postmenopausal for at least 1 year, or surgically sterile (bilateral oophorectomy or hysterectomy).

All subjects with potential risk of pregnancy (male or female) must use highly effective contraception with a failure rate <1% during treatment and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).

Критерии исключения

• Patients meeting any of the following criteria are not eligible for this study:

Presence of EGFR, ALK, ROS1, or other actionable mutations excluding MET. Receipt of live attenuated vaccines within 4 weeks prior to enrollment or planned during the study period.

• All participants must undergo brain imaging (MRI or contrast-enhanced CT) prior to enrollment to rule out brain metastases.
• Major surgery (e.g., thoracic, abdominal, or pelvic) within 4 weeks prior to study treatment initiation, or ongoing recovery from surgical complications.

Diagnosis of any malignancy other than NSCLC within 5 years prior to study treatment initiation (excluding completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ carcinoma, or completely resected papillary thyroid carcinoma).

• Active, known, or suspected autoimmune disease.
• Known history of primary immunodeficiency.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to the study drug bozitinib, platinum-based doublet chemotherapy, or any excipients.
• Not fully recovered from any toxicity and/or complications caused by prior interventions (i.e., ≤ Grade 1 or returned to baseline, excluding fatigue or alopecia) prior to study treatment.
• Untreated active hepatitis B infection (defined as HBsAg positive with detectable HBV-DNA above the upper limit of normal at the local laboratory).

Note: Patients with hepatitis B meeting the following criteria may be enrolled:

HBV viral load <1000 copies/mL (200 IU/mL) prior to first dose; patients must receive antiviral therapy throughout chemotherapy to prevent viral reactivation.

Patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-) do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation.

• Active hepatitis C infection (HCV antibody positive and HCV-RNA above the assay lower limit of detection).
• Any history, condition, treatment, or laboratory abnormality that could interfere with study results, hinder full participation, or that the investigator considers a potential risk or inappropriate for enrollment.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07153770 · 2025LY0214

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗