Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC

NCT ID: NCT06127303

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-02
• Study Completion Date: 2028-04-02

Brief Summary

Immunotherapy with programmed death-1(PD-1) inhibitors is now standard therapy for first-line use in patients with driver-negative advanced NSCLC, whether as single-agent or in combination with chemotherapy. After progression of first-line immunotherapy, NSCLC patients may be treated with chemotherapy, radiotherapy or targeted therapies, among others. Recently, Immune Checkpoint inhibitors (ICIs) rechallenge has become a highly anticipated option. Although the objective response rate of the ICIs rechallenge patients has decreased substantially compared with the efficacy of the first ICI treatment, nearly 50% of patients can regain disease control.

Cryoablation is a minimally invasive technique that utilizes very low temperature to eliminate viable tumour cells in target tissues. It has been reported that ablation can enhance immune response.

The objective of this study was to evaluate the efficacy and safety of toripalimab (PD-1) in combination with cryoablation in the treatment of oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Toripalimab Combined with Cryoablation

Patients with oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress would be treated with Toripalimab Combined with Cryoablation.

Group Type: EXPERIMENTAL

Toripalimab

Intervention Type: DRUG

Toripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after cryoablation, until occurrence of termination event specified in the protocol.

Cryoablation

Intervention Type: OTHER

The ablation was performed on the first day of each cycle, and the target lesions were comprehensively screened for cryoablation based on the location and size of the lesions.

Interventions

Toripalimab

Toripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after cryoablation, until occurrence of termination event specified in the protocol.

Intervention Type: DRUG

Cryoablation

The ablation was performed on the first day of each cycle, and the target lesions were comprehensively screened for cryoablation based on the location and size of the lesions.

Intervention Type: OTHER

Other Intervention Names

Immunotherapy

Eligibility Criteria

Inclusion Criteria

• Voluntary participation and written informed consent;
• histologically or cytologically confirmed advanced metastatic (stage IV) non-small cell lung cancer;
• Patients with negative driver genes who develop oligoprogression after receiving standard first-line therapy. The oligoprogression is defined as: 1-5 metastatic lesions, and no more than 3 organs;
• Age 18-75 years old; ECOG PS: 0-1; The expected survival is more than 3 months;
• At least one measurable lesion;
• Patients were willing to provide adequate blood and tissue samples；
• Patients had adequate hematologic, renal, and liver function;
• International normalised ratio (INR) ≤1.5 and partial thromboplastin time (PTT or aPTT) ≤1.5 x ULN within 7 days prior to study treatment;
• The woman patients of childbearing age who must agree to take contraceptive methods during the research;
• The man patients who must agree to take contraceptive methods during the research and within another 6 months after it.

Exclusion Criteria

• cytologically or histologically confirmed combination with small cell lung cancer component or sarcomatoid element;
• Previously received targeted therapy for advanced NSCLC (including osimertinib, erlotinib, crizotinib, etc);
• Had undergone major surgical operations or had not fully recovered from previous operations within 3 weeks before enrollment;
• Known active nervous system (CNS) metastases and/or carcinomatous meningitis;
• Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; patients with stable symptoms after drainage can be enrolled;
• History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening;
• Clinically uncontrolled active infection, including but not limited to acute pneumonia;
• Uncontrollable major epileptic seizure or superior vena cava syndrome;
• Previous or current co-occurrence of other malignancies (excluding controllable non-melanoma basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast or cervix, superficial bladder cancer, or other carcinoma in situ);
• Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease;
• Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening;
• Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle;
• Vaccination of live-virus vaccine within 30 days after the start of planned treatment; Inactivated seasonal influenza vaccine was permitted;
• Patients has HIV-positive;
• Patients judged by the investigator to be inappropriate as a subject of this study.
• History of severe allergic, quasi-allergic, or other hypersensitive reactions to chimeric or humanized antibodies or fusion proteins;
• Known allergy to biological drugs produced from Chinese hamster ovary cells, or to citrate monohydrate, sodium citrate dihydrate, mannitol, polysorbate (components of the study drug);
• Patients who have previously received allogeneic stem cells or parenchymal organ transplants.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ziming Li

Deputy Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Ziming Li, Doctor

Role: CONTACT

liziming1980@163.com

0086-13764590226

Facility Contacts

Ziming Li, Doctor

Role: primary

liziming1980@163.com

0086-13764590226

Xi Liang, MD,PHD

Role: primary

aihuabao312@126.c0m

+8613501814090

Yong Zhang, MD,PHD

Role: primary

zhang.yong@zs-hospital.sh.cn

+8615000229853

Other Identifiers

IS23070

Identifier Type: -

Identifier Source: org_study_id