Multicenter, Single-Arm, Prospective Phase II Study of Neoadjuvant Cryo-Thermal Ablation Combined With Toripalimab and Chemotherapy for Resectable Stage IB-IIIB Non-Small Cell Lung Cancer

NCT07855965 | Recruiting Phase 2

• 1 other identifier: NEOCTATC-2026-09
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 9

Brief Summary

Neoadjuvant chemoimmunotherapy has improved outcomes in patients with resectable non-small cell lung cancer (NSCLC), but a substantial proportion of patients do not achieve a major pathological response. Cryo-Thermal Ablation may induce immunogenic tumor cell death and remodel the tumor immune microenvironment, potentially enhancing the antitumor activity of subsequent chemoimmunotherapy. This multicenter, single-arm, open-label, prospective Phase II study will evaluate the efficacy and safety of CT-guided Cryo-Thermal Ablation followed by toripalimab plus platinum-based doublet chemotherapy as neoadjuvant treatment for patients with resectable stage IB-IIIB NSCLC. For stage IB disease, only patients with cT2aN0M0 disease and a maximum primary tumor diameter of 4.0 cm are eligible. Patients with more advanced disease must be considered resectable by multidisciplinary team assessment according to the study protocol. Approximately 40 participants will receive Cryo-Thermal Ablation followed by 3 planned cycles of toripalimab plus platinum-based doublet chemotherapy and subsequent curative-intent surgical resection. The primary outcome is the pathological complete response (pCR) rate. Secondary outcomes include major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, event-free survival (EFS), overall survival (OS), treatment-emergent adverse events (TEAEs), and health-related quality of life. Exploratory translational analyses will investigate treatment-associated local and systemic antitumor immune responses and molecular dynamics using spatial transcriptomics, T-cell receptor sequencing, tumor genomic profiling, circulating tumor DNA analysis, imaging mass cytometry, and exploratory intratumoral metagenomic and metabolomic profiling.

Conditions

Carcinoma, Non-Small-Cell Lung (NSCLC)

Keywords

Neoadjuvant therapy; Resectable non-small cell lung cancer; Ablation; Toripalimab; PD-1 inhibitor; Chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The proportion of enrolled participants who achieve pathological complete response (pCR), defined as no residual viable tumor cells in the resected primary tumor and all sampled regional lymph nodes after neoadjuvant treatment (ypT0N0). Participants who do not undergo surgical resection or for whom pathological response cannot be adequately assessed will not be considered to have achieved pCR in the primary efficacy analysis.

  At pathological evaluation of the surgical resection specimen, with surgery planned approximately 4-6 weeks after the final neoadjuvant treatment.

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  At preoperative radiographic reassessment, approximately 4-6 weeks after the final neoadjuvant treatment.

• Major Pathological Response (MPR) Rate

  At pathological evaluation of the surgical resection specimen, with surgery planned approximately 4-6 weeks after the final neoadjuvant treatment.

• R0 resection rate

  At surgical and pathological evaluation of the resection specimen, with surgery planned approximately 4-6 weeks after the final neoadjuvant treatment.

• Event-Free Survival (EFS)

  From enrollment until the first EFS event, death, last disease assessment, or end of follow-up, up to approximately 5 years.

• Overall Survival (OS)

  From enrollment until death from any cause or the end of follow-up, up to approximately 5 years.

Other Outcomes (7)

• Changes in the Spatial Tumor Immune Microenvironment Assessed by Atera In Situ Spatial Transcriptomics

  Baseline tumor biopsy before Cryo-Thermal Ablation and surgical resection approximately 4-6 weeks after the final neoadjuvant treatment.

• Changes in Peripheral and Tumor T-cell Receptor Clonality Assessed by Bulk TCR Sequencing

  Peripheral blood: baseline; Day 14 after ablation before Cycle 1; before Cycle 2 (approximately Day 35) and Cycle 3 (approximately Day 56); and preoperative assessment 4-6 weeks after Cycle 3. Tumor tissue: baseline biopsy and surgical resection.

• Tumor Genomic Alterations Assessed by a 919-Gene Next-Generation Sequencing Panel

  Baseline tumor biopsy before Cryo-Thermal Ablation.

Study Arms (1)

Neoadjuvant Cryo-Thermal Ablation Combined With Toripalimab and Platinum-Based Doublet Chemotherapy

EXPERIMENTAL

Participants will receive CT-guided Cryo-Thermal Ablation followed by 3 planned cycles of toripalimab plus histology-appropriate platinum-based doublet chemotherapy administered every 3 weeks, followed by curative-intent surgical resection after preoperative reassessment.

Procedure: Cryo-Thermal Ablation; Drug: Toripalimab; Drug: Platinum-based doublet chemotherapy

Interventions

Cryo-Thermal Ablation PROCEDURE

Cryo-Thermal Ablation is a CT-guided percutaneous local ablation procedure performed on the primary lung tumor before initiation of neoadjuvant systemic therapy. Under CT guidance, one or more ablation probes are placed percutaneously into the target lesion. Sequential cryogenic and thermal treatment is delivered according to the study protocol and device operating instructions. Technical parameters, including probe placement, treatment cycles, treatment duration, and target temperatures, will be standardized according to the protocol.

Also known as: Ablation

Neoadjuvant Cryo-Thermal Ablation Combined With Toripalimab and Platinum-Based Doublet Chemotherapy

Toripalimab DRUG

Toripalimab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, will be administered intravenously at a dose of 240 mg every 3 weeks (q3w) in combination with platinum-based doublet chemotherapy for 3 planned cycles following Cryo-Thermal Ablation. Dose interruption, delay, or discontinuation will be permitted when clinically indicated for treatment-related toxicity.

Neoadjuvant Cryo-Thermal Ablation Combined With Toripalimab and Platinum-Based Doublet Chemotherapy

Platinum-based doublet chemotherapy DRUG

Participants will receive protocol-specified platinum-based doublet chemotherapy in combination with toripalimab every 3 weeks for 3 planned cycles following Cryo-Thermal Ablation. The specific regimen will be selected according to tumor histology and the study protocol. Chemotherapy dosing, administration, dose modification, and supportive treatment will follow the protocol-defined regimen and standard clinical practice. After neoadjuvant therapy, disease reassessment will be performed before curative-intent surgical resection.

Neoadjuvant Cryo-Thermal Ablation Combined With Toripalimab and Platinum-Based Doublet Chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis, Stage, and Resectability
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Clinical stage IB-IIIB according to the 9th edition IASLC/AJCC TNM classification.
• For stage IB disease, only patients with a maximum tumor diameter of 4.0 cm (cT2aN0M0) are eligible.
• The disease must be considered resectable by multidisciplinary team (MDT) assessment with curative-intent surgery planned after neoadjuvant treatment.
• The primary lung lesion must be technically amenable to percutaneous biopsy and CT-guided Cryo-Thermal Ablation..
• No prior systemic or local anti-tumor therapy for the current NSCLC.
• Age, Performance Status, and General Condition
• Age 18-80 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy \>6 months.
• Able to understand and voluntarily sign the informed consent form and willing to comply with study treatment, specimen collection, and follow-up requirements.
• Tumor Tissue and Pulmonary Function
• Willing to provide tumor tissue and blood samples required by the study protocol.
• Adequate pulmonary function for the planned treatment and subsequent pulmonary resection, including: FEV1 ≥1.2 L or ≥50% of predicted value; and predicted postoperative FEV1≥30% of predicted value.

You may not qualify if:

• Histological or Molecular Characteristics
• Small-cell lung cancer (SCLC) or mixed histology containing a small-cell component.
• Presence of protocol-defined actionable oncogenic alterations detected by tumor tissue and/or plasma-based molecular testing, including:
• EGFR sensitizing or protocol-defined activating alterations, including exon 19 deletion, L858R, G719X, S768I, L861Q, or exon 20 insertion;
• ALK rearrangement;
• ROS1 rearrangement;
• MET exon 14 skipping alteration or protocol-defined MET amplification;
• KRAS G12C;
• BRAF V600E;
• NTRK1/2/3 fusion;
• RET rearrangement; or HER2 alteration as defined in the study protocol.
• Contraindications to Percutaneous Biopsy or Cryo-Thermal Ablation
• Active clinically significant hemoptysis, defined as ≥1/2 teaspoon of fresh blood, within 2 weeks before the planned procedure.
• Clinically significant bleeding tendency or coagulation disorder that cannot be adequately corrected before biopsy or ablation.
• Therapeutic anticoagulant or vitamin K antagonist treatment that cannot be safely interrupted or managed during the periprocedural period according to the study protocol and institutional practice. Stable anticoagulation may be permitted when appropriate periprocedural interruption or management is considered safe by the investigator.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (9)

The Third People's Hospital of Chengdu

Chengdu, Sichuan, 610031, China

NOT YET RECRUITING

Sichuan Cancer Hospital & Institute

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Public Health Clinical Center of Chengdu

Chengdu, Sichuan, 610066, China

NOT YET RECRUITING

The Affiliated Hospital of Southwest Medical University

Luzhou, Sichuan, 646000, China

NOT YET RECRUITING

Meishan People's Hospital

Meishan, Sichuan, 620010, China

NOT YET RECRUITING

Affiliated Hospital of North Sichuan Medical College

Nanchong, Sichuan, 637000, China

NOT YET RECRUITING

Suining Central Hospital

Suining, Sichuan, 629000, China

NOT YET RECRUITING

Zigong Fourth People's Hospital

Zigong, Sichuan, 643000, China

NOT YET RECRUITING

Related Publications (5)

• Mooradian MJ, Fintelmann FJ, LaSalle TJ, Simon J, Graur A, Muzikansky A, Mino-Kenudson M, Shalhout S, Kaufman HL, Jenkins RW, Lawrence D, Lawless A, Sharova T, Uppot RN, Fang J, Blaum EM, Gonye ALK, Gushterova I, Boland GM, Azzoli C, Hacohen N, Sade-Feldman M, Sullivan RJ. Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial. Nat Commun. 2024 Aug 27;15(1):7357. doi: 10.1038/s41467-024-51722-x.

  PMID: 39191779 BACKGROUND

• Gu S, Luo Q, Zhang Y, Qian L, Chen K, Liang F, Hu Y, Zhou R, Wang Y, Liu J, Ning Z, Xu L, Meng Z, Li Y, Wang P. Cryoablation plus sintilimab and lenvatinib in advanced or metastatic intrahepatic cholangiocarcinoma: a phase 2 trial. Nat Cancer. 2026 Jan;7(1):60-79. doi: 10.1038/s43018-025-01058-2. Epub 2025 Nov 1.

  PMID: 41176543 BACKGROUND

• Lu S, Zhang W, Wu L, Wang W, Zhang P; Neotorch Investigators; Fang W, Xing W, Chen Q, Yang L, Mei J, Tan L, Sun X, Xu S, Hu X, Yu G, Yu D, Yang N, Chen Y, Shan J, Xing L, Tian H, Zhang X, Zhou M, Fang H, Wu G, Liu Y, Ye M, Cao L, Jiang J, Li X, Zhu L, Li S, Kang M, Zhong A, Chen K, Wu N, Sun Q, Ma H, Cai K, Wang C, Lin G, Zhu K, Zhang Y, Zhang X, Hu H, Zhang W, Chen J, Yang Z, Hang X, Hu J, Huang Y, Zhang Z, Zhang L, Zhang L, Liu L, Lin D, Zhang J, Chen G, Li Y, Zhu L, Wang W, Yu W, Cao D, Keegan P, Yao S. Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial. JAMA. 2024 Jan 16;331(3):201-211. doi: 10.1001/jama.2023.24735.

  PMID: 38227033 BACKGROUND

• Liu Z, Yang Z, Wu J, Zhang W, Sun Y, Zhang C, Bai G, Yang L, Fan H, Chen Y, Zhang L, Jiang B, Liu X, Ma X, Tang W, Liu C, Qu Y, Yan L, Zhao D, Wu Y, He S, Xu L, Peng L, Chen X, Zhou B, Zhao L, Zhao Z, Tan F, Zhang W, Yi D, Li X, Gao Q, Zhang G, Wang Y, Yang M, Fu H, Guo Y, Hu X, Cai Q, Qi L, Bo Y, Peng H, Tian Z, She Y, Zou C, Zhu L, Cheng S, Zhang Y, Zhong W, Chen C, Gao S, Zhang Z. A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer. Cell. 2025 May 29;188(11):3081-3096.e19. doi: 10.1016/j.cell.2025.03.018. Epub 2025 Mar 26.

  PMID: 40147443 BACKGROUND

• Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol. 2023 Sep;20(9):624-639. doi: 10.1038/s41571-023-00798-3. Epub 2023 Jul 21.

  PMID: 37479810 BACKGROUND

MeSH Terms

Conditions

Carcinoma; Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Beinuo Wang, MD

CONTACT

+86-191-0807-4950; wang_beinuo@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director & Medical Team Leader, Department of Thoracic Surgery, West China Hospital, Sichuan University; Associate Professor of Surgery; Master's Supervisor

Study Record Dates

• First Submitted: September 9, 2026
• First Posted: October 2, 2026
• Study Start: September 10, 2026
• Primary Completion (Estimated): August 5, 2028
• Study Completion (Estimated): August 5, 2033
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)