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

Inclusion Criteria:

1. Signed an informed consent form
2. Patients aged ≥18
3. 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:

   1. 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.
   2. Contralateral or supraclavicular lymph node metastasis (N3): This includes contralateral hilar and mediastinal lymph node metastasis, or ipsilateral/contralateral supraclavicular lymph node metastasis.
   3. 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.
   4. 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.
   5. 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.
   6. Patient unable to tolerate lobectomy or pneumonectomy: Insufficient cardiopulmonary reserve, severe cardiovascular disease, coagulation dysfunction, or other systemic diseases precluding lobectomy or pneumonectomy.
4. at least one measurable lesion according to RECIST 1.1 criteria
5. ECOG PS 0-1.
6. Pulmonary function must meet: FEV1 \> 1.0 L and FEV1%\> 40%
7. appropriate organ function

Exclusion Criteria:

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