Multimodal Ablation Combined With Perioperative Tislelizumab and Chemotherapy for Resectable II-IIIB NSCLC

This is a prospective, open-label, single-center, single-arm phase II clinical trial evaluating the efficacy and safety of multimodal ablation in combination with perioperative tislelizumab and chemotherapy in patients with pathologically confirmed resectable stage II-IIIB (N2) non-small cell lung cancer (NSCLC).

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC
• Intervention / Treatment: Device: Multimodal Ablation; Drug: Neoadjuvant therapy; Procedure: Surgery; Drug: Adjunctive therapy

Detailed Description

Eligible patients will receive multimodal ablation, followed by perioperative tislelizumab in combination with platinum-based doublet chemotherapy, and subsequently undergo radical surgical resection. Adjuvant tislelizumab will be continued after surgery.The primary endpoint is the pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, event-free survival (EFS), overall survival (OS), and safety.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years, either gender;
• Pathologically confirmed stage II-IIIB (N2) squamous or non-squamous non-small cell lung cancer (NSCLC) according to the 9th edition of the AJCC/UICC NSCLC staging system;
• Presence of lesions suitable for ablation therapy confirmed by imaging evaluation;
• Evaluated as resectable with R0 resection before enrollment, and consent to undergo radical surgical resection;
• ECOG performance status score of 0-1;
• Eligible for platinum-based doublet chemotherapy;
• Adequate cardiopulmonary function to meet the requirements of curative surgical resection;

• Sufficient organ function confirmed by laboratory tests within 28 days before enrollment:

  • Blood routine: WBC >= 3.0×10^9/L; ANC >= 1.5×10^9/L; PLT >= 100×10^9/L; HGB >= 90 g/L.
  • Liver function: AST <= 5.0×ULN; ALT <= 5.0×ULN; TBIL <= 1.5×ULN;
  • Renal function: Cr <= 1.5×ULN;
  • For patients receiving cisplatin: creatinine clearance >= 60 mL/min.
  • For patients receiving carboplatin: creatinine clearance >= 45 mL/min.
  • Coagulation function: INR <= 1.5×ULN (<=3×ULN for patients on anticoagulants; anticoagulants must be discontinued for one week before ablation); APTT <= 1.5×ULN;
• Fully understand the study and voluntarily sign the informed consent form (ICF).

Exclusion Criteria:

• Tumor is adjacent to the hilum, invades major blood vessels, or has contraindications for surgery;
• History of interstitial lung disease, non-infectious pneumonia, or uncontrolled pulmonary diseases including pulmonary fibrosis and acute lung disease;
• Previous allogeneic stem cell transplantation or organ transplantation;
• Previous radiotherapy or chemotherapy;
• Previous local treatment (e.g., radioactive seed implantation, ablation) for the target ablation lesion;
• Previous treatment with immune checkpoint inhibitors, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies;
• Complicated with severe cardiac, pulmonary, hepatic, renal insufficiency, or coagulation disorders;
• Clinically significant cardio-cerebrovascular diseases, including but not limited to acute myocardial infarction within 6 months before enrollment, heart failure of NYHA class III or IV, ventricular arrhythmia ≥ grade 2, any history of cerebrovascular accident;
• Underwent any major surgical procedure requiring general anesthesia within 28 days before enrollment;
• Previous severe immune system diseases or active infection;
• Pregnant or lactating female;
• Complicated with other malignancies (un cured within 5 years);
• Confirmed positive EGFR or ALK driver genes by genetic testing;
• Any condition requiring systemic therapy with corticosteroids (>10 mg prednisone per day or equivalent) or other immunosuppressive drugs before enrollment;
• Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis;
• Known history of HIV infection;
• Untreated chronic hepatitis B patients, chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL, or active hepatitis C virus (HCV) patients; (Note: Inactive hepatitis B surface antigen carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL), and cured hepatitis C patients are eligible.);
• Received live vaccine within 28 days before enrollment;
• Simultaneously participating in another therapeutic clinical study;
• Other conditions considered unsuitable for participation in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multimodal Ablation Combined with Perioperative Tislelizumab and Chemotherapy; Patients in this single arm will receive a multimodal ablation procedure, followed by perioperative tislelizumab in combination with platinum-based doublet chemotherapy , and subsequently undergo radical surgical resection. Adjuvant tislelizumab will be continued after surgery as per protocol.

Device: Multimodal Ablation; CT-guided preoperative multimodal ablation performed with multimodal tumor therapy system.Target lung lesions are ablated within 2 weeks after subject enrollment.; Drug: Neoadjuvant therapy; Neoadjuvant tislelizumab (200 mg, IV, Q3W) combined with chemotherapy will be administered within 2 weeks after ablation. For patients with squamous NSCLC, cisplatin or carboplatin combined with paclitaxel will be used; for patients with non-squamous NSCLC, cisplatin or carboplatin combined with pemetrexed will be used, for a total of 3-4 cycles of treatment.; Other Names: Tislelizumab; Procedure: Surgery; Surgical resection will be performed within 4-6 weeks after the last neoadjuvant treatment. The pulmonary lesions (including the ablated lesions) will be radically resected via surgery.; Drug: Adjunctive therapy; Adjuvant therapy will be initiated within 2-8 weeks after surgery. Postoperative adjuvant therapy with tislelizumab (400 mg, Q6W) will be maintained for up to 1 year. Concomitant chemotherapy is allowed during this period based on guidelines/consensus or multidisciplinary team (MDT) discussion.; Other Names: Tislelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response Rate	Proportion of patients with no residual viable tumor cells in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant therapy.	Perioperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response Rate	Proportion of patients with ≤10% residual viable tumor cells in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant therapy. Assessed by pathologist within 2 weeks after surgical resection.	Perioperative
Event-Free Survival	Time from start of treatment to the first occurrence of any of the following events: disease progression precluding surgical treatment, local or distant recurrence, or death from any cause. Patients without an event are censored at the date of last imaging assessment.	Through study completion, up to 5 years
Overall Survival	Time from enrollment to death due to any cause. Patients alive at last follow-up are censored at the last follow-up date. Lost-to-follow-up patients are censored at the last confirmed survival date.	Through study completion, up to 5 years
Incidence and Severity of Adverse Events and Serious Adverse Events	Safety will be assessed by monitoring the incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs) graded according to NCI-CTCAE v6.0.	Through study completion

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Combined Modality Therapy; Surgical Procedures, Operative; Neoadjuvant Therapy; tislelizumab
• Other Study ID Numbers: NCP1-1111

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No