Bozitinib Combined With Chemotherapy as Radical Treatment... | NCT07153770

NCT07153770

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bozitinib group	Experimental	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 markers, and imaging results, if molecular abnormalities are detected., patients will receive bozitinib within 3 months after surgery. If CEA remains within the normal range and blood cfDNA-MRD is negative, patients will enter a regular follow-up program, with MRD assessments every 3 months during the first 2 years and every 6 months from years 3 to 5. If MRD conversion to positive, abnormal CEA, or abnormal CT findings occur within 5 within 5 years, bozitinib will be administered.	Drug: Bozitinib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bozitinib	Drug	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 markers, and imaging results, if molecular abnormalities are detected., patients will receive bozitinib within 3 months after surgery. If CEA remains within the normal range and blood cfDNA-MRD is negative, patients will enter a regular follow-up program, with MRD assessments every 3 months during the first 2 years and every 6 months from years 3 to 5. If MRD conversion to positive, abnormal CEA, or abnormal CT findings occur within 5 within 5 years, bozitinib will be administered.

Measure	Description	Time Frame
Major Pathological Response	defined as the proportion of patients who achieve a major pathological response among all patients undergoing surgical pathological assessment. Major pathological response is defined as ≤10% viable tumor cells in the resected primary tumor and regional lymph nodes, as assessed by hematoxylin and eosin (H&E) staining.	Up to 6 month

Measure	Description	Time Frame
Objective Response Rate	defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) among all patients.	Up to 6 month
Pathological Complete Response rate

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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).

Exclusion Criteria:

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.