Safety and Efficacy of Cryoablation With Karelizumab and Apatinib for Multiple Lung Cancers

Inclusion Criteria:

1. Clinical and pathological diagnosis of multiple primary lung cancers；

2. There were 3 intrapulmonary nodules ≥ the initial diagnosis or preoperative, andthere was no lymph node metastasis；

3. The maximum lesion diameter ≤ 3 cm；

4. At most, patients has undergone surgical resection treatment, and there are ≥ 2remaining intrapulmonary nodules, and the postoperative pathology confirms that itis MIA or AIS；

5. It is estimated that at least 1 measurable lesion meeting RECIST v1.1 criteria willremain after cryotherapy；

6. Male or female≥ 18 years old and ≤ 75 years old；

7. United States Eastern Cooperative Oncology Group Performance Status (ECOG PS) scoreof 0 or 1；

8. Expected survival ≥ 12 weeks；

9. Vital organ and bone marrow function meets the following requirements:a.Bloodroutine: absolute neutrophil count (ANC) ≥1.5× 109/L, platelet (PLT) ≥100× 109/L,hemoglobin (HGB) ≥9 g/dL;b.Liver function: serum total bilirubin (TBIL) ≤1.5 timesthe upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartateaminotransferase (AST) ≤2.5 times the ULN, serum albumin (ALB) ≥2.8 g/dL;c.Renalfunction: serum creatinine (Cr) ≤ 1.5 x ULN, or creatinine clearance ≥ 40 mL/min;

10. Subject with subject sexual partner needs to use one medically approvedcontraceptive measure (such as intrauterine device, birth control pill or condom,etc.) during study treatment and for 6 months after the end of the study treatmentperiod;

11. Subjects must have signed an IRB/IEC-approved written informed consent form inaccordance with competent authority and study site guidelines and be able to complywith protocol-specified visits, treatment protocols, laboratory tests, and relatedprocedures.

Exclusion Criteria:

1. Patients with known EGFR mutations, ALK rearrangements;

2. Conditions that cannot be treated with cryoablation: diffuse lesions in both lungs,extensive pleural metastases with large pleural effusions, tumors adjacent to orencircling large mediastinal vessels, etc;

3. Prior receipt of anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, or any otherantibody or drug targeting T cell co-stimulation or immune checkpoint pathways;

4. Received the following treatments:a.Received systemic anti-tumor therapy such aschemotherapy, targeted therapy, immunotherapy, etc. within 4 weeks prior torandomization;b.Treatment with any investigational drug within 4 weeks prior torandomization;c.Receipt of high-dose immunosuppressive medications (systemicglucocorticoids greater than 10 mg/day of prednisone or its equivalent) within 4weeks prior to randomization;d.Major surgery (such as open, thoracotomy, orlaparotomy, etc.), or unhealed surgical wounds, ulcers, or fractures within 4 weeksprior to randomization.

5. Known or suspected active autoimmune disease (congenital or acquired);

6. Known allogeneic organ transplantation (other than corneal transplantation) orallogeneic hematopoietic stem cell transplantation;

7. Hypersensitivity to any component of the monoclonal antibody preparation;

8. With interstitial lung disease;

9. With other uncontrolled serious medical conditions;

10. Other acute or chronic illness, psychiatric illness, or abnormal laboratory testvalues that may result in an increase in the risk associated with studyparticipation or study drug administration, or interfere with the interpretation ofstudy results, and the patient is listed as ineligible for this study in thejudgment of the investigator.