Iparomlimab and Tuvonralimab Plus Chemotherapy for Inducing Conversion to Resectability in Initially Unresectable Stage III NSCLC

Inclusion criteria

• Signed an informed consent form
• Patients aged ≥18
• Histologically or cytologically confirmed Stage III (AJCC 9th ed.) squamous or non-squamous NSCLC (mixed tumors classified by predominant cell type), deemed unresectable by the MDT team based on at least one of the following criteria:

• Ipsilateral multi-station or confluent mediastinal lymph node metastasis: Imaging shows ipsilateral multi-station lymph node metastasis or confluent lymph node mass (>3cm diameter) or invasion of surrounding organs, making complete surgical clearance impossible.
• Contralateral or supraclavicular lymph node metastasis (N3): This includes contralateral hilar and mediastinal lymph node metastasis, or ipsilateral/contralateral supraclavicular lymph node metastasis.
• Invasion of vital organs or major vessels: Anatomical tumor or lymph node invasion directly involving the heart, major vessels (e.g., aorta, main pulmonary artery), trachea, esophagus, vertebral body (>50% involvement), or brachial plexus.
• Extensive chest wall and pleural invasion: Involvement of ribs, intercostal muscles, and chest wall soft tissues is extensive, requiring large chest wall resection that the patient's pulmonary function cannot tolerate, or impossible to clear surgically.
• Special anatomical location: e.g., superior sulcus tumor (Pancoast tumor) invading vertebrae/nerve plexus, recurrent laryngeal nerve involvement causing vocal cord paralysis, tumor extent precluding R0 resection.
• Patient unable to tolerate lobectomy or pneumonectomy: Insufficient cardiopulmonary reserve, severe cardiovascular disease, coagulation dysfunction, or other systemic diseases precluding lobectomy or pneumonectomy.
• at least one measurable lesion according to RECIST 1.1 criteria
• ECOG PS 0-1.
• Pulmonary function must meet: FEV1 > 1.0 L and FEV1%> 40%
• appropriate organ function

Exclusion criteria

• NSCLC with small cell component identified on pathology (regardless of proportion); Histological types of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC-NOS.
• Known EGFR mutation or ALK rearrangement positivity (eligibility of subjects with other driver gene positivity will be determined by the project biomarker expert group).
• Prior systemic anti-tumor therapy or thoracic radiotherapy.