Efficacy and Safety of Combination Therapy of Sintilimab and Chemotherapy with Cryoablation in the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC): a pilot study protocol for a single center, single arm, phase II study (Preprint)

Abstract

Immunotherapy has significantly advanced lung cancer treatment, particularly in non-squamous non-small cell lung cancer (NSCLC), with overall response rates between 50%-60%. However, about 30% of patients only achieve stable disease. 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.

This study aims to investigate the efficacy and safety of immuno-chemotherapy in combination of cryoablation as the first-line treatment of advanced NSCLC.

This is a phase II, pilot, open-label, single arm, single center, interventional study. Patients with stage IIIB-IIIC or IV NSCLC with T staging ranging from T1 to T2b will receive sintilimab (200mg/ m2, ivgtt, q3w) and chemotherapy. After two cycles, the feasibility of cryoablation is considered for those with stable disease by multidisciplinary team. Cryoablation with three freezing-thawing cycles will be performed for main lesion. The third cycle of systemic therapy begins 7±3 days after cryoablation. A total of 20 patients will be enrolled. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, other discontinuation criterion is met, or study completion. The primary objective is to assess Progression-Free Survival (PFS). The secondary objective is to assess the efficacy through, Duration of Response (DoR), Disease Control Rate (DCR), Overall Survival (OS) and safety profile. The exploratory objective is to investigate the immune factor change after two cycles of immune-chemotherapy, and at 1, 3, and 7 days after cryoablation. Any adverse events that occur during the trial will be promptly recorded.

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.

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

NCT06483009