Efficacy and Safety of a Therapy Combining Sintilimab and Chemotherapy With Cryoablation in the First-Line Treatment of Advanced Nonsquamous Non-Small Cell Lung Cancer: Protocol for a Phase II, Pilot, Single-Arm, Single-Center Study.

Background: Immunotherapy has significantly advanced lung cancer treatment, particularly in nonsquamous non-small cell lung cancer (NSCLC), with overall response rates between 50% and 60%. However, about 30% of patients only achieve a stable disease state. Cryoablation has shown potential to enhance immunotherapy by modifying the tumor's immune microenvironment through the release of antigens and immune factors. Addressing how to boost the immune response in these patients is critical.

Objective: This study aims to investigate the efficacy and safety of immunochemotherapy in combination with cryoablation as a first-line treatment for advanced NSCLC.

Methods: This is a phase II, pilot, open-label, single arm, single center, interventional study. Patients with stage IIIB to IIIC or IV NSCLC with T staging ranging from T1 to T2b will receive sintilimab (200 mg/m² every 3 weeks) and chemotherapy. After 2 cycles, the feasibility of cryoablation will be considered for those with stable disease by a multidisciplinary team. Cryoablation with 3 freeze-thaw cycles will be performed for the main lesion. The third cycle of systemic therapy will begin 7 (SD 3) days after cryoablation. A total of 20 patients will be enrolled. Treatment will continue until the disease progresses, there is unacceptable toxicity, a participant withdraws consent, other discontinuation criteria are met, or the study reaches completion. The primary objective is to assess progression-free survival (PFS). The secondary objective is to assess efficacy through duration of response, disease control rate, overall survival (OS), and the safety profile. The exploratory objective is to investigate and compare immune factor changes after 2 cycles of immunochemotherapy and at 1, 3, and 7 days after cryoablation. Survival time will be estimated using the Kaplan-Meier method to calculate median PFS and OS. Any adverse events that occur during the trial will be promptly recorded.

Results: The project was funded in 2024, and enrollment will be completed in 2025. The first results are expected to be submitted for publication in 2027.

Conclusions: This study will provide evidence for the efficacy and safety of the combination of immunochemotherapy and cryoablation as a first-line treatment for advanced NSCLC. Although it has a limited sample size, the findings of this study will be used in the future to inform the design of a fully powered, 2-arm, larger-scale study.

Trial registration: ClinicalTrials.gov NCT06483009; https://clinicaltrials.gov/study/NCT06483009.

International registered report identifier (irrid): PRR1-10.2196/64950.