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

NCT06127303 | Recruiting Phase 2

• 1 other identifier: IS23070
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

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

Keywords

Oligo-progression; Toripalimab; Cryoablation

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death, whichever occurred first.

  6 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  6 months

• Disease control rate (DCR)

  6 months

• Overall Survival (OS)

  24 months

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Up to 2 years

• Correlation analysis of PD-L1 expression of tumor and ORR

  Up to 1 years

Study Arms (1)

Toripalimab Combined with Cryoablation

EXPERIMENTAL

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

Drug: Toripalimab; Other: Cryoablation

Interventions

Toripalimab DRUG

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

Also known as: Immunotherapy

Toripalimab Combined with Cryoablation

Cryoablation 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.

Toripalimab Combined with Cryoablation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (3)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

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

Shanghai, China

NOT YET RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab; Immunotherapy; Cryosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Ziming Li, Doctor

CONTACT

0086-13764590226; liziming1980@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

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 13, 2023
• Study Start: April 2, 2024
• Primary Completion: April 2, 2026
• Study Completion (Estimated): April 2, 2028
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)