Combining Toripalimab with Cryoablation for Advanced Lung Cancer Treatment

A Single-arm, Phase II Clinical Study of Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC

This study is testing if combining a new immune therapy called toripalimab with a freezing treatment can help people with advanced lung cancer who have had limited growth after their first treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Chest Hospital (Academic / other)
• Drugs / interventions: osimertinib, erlotinib, crizotinib, toripalimab, chemotherapy, Immunotherapy
• Locations: 3 sites (Shanghai, Shanghai Municipality and 2 other locations)
• Trial ID: NCT06127303 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of toripalimab, a PD-1 inhibitor, in combination with cryoablation for patients with driver-negative advanced non-small cell lung cancer (NSCLC) who experience oligoprogression after first-line therapy. The study aims to determine if this combination can enhance immune response and improve disease control in patients with limited metastatic lesions. Participants will undergo treatment and be monitored for outcomes related to tumor response and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with advanced metastatic NSCLC who have experienced oligoprogression after first-line therapy and have negative driver genes.

Not a fit: Patients with driver-positive NSCLC or those who do not meet the oligoprogression criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option that enhances disease control for patients with advanced NSCLC.

How similar studies have performed: While the combination of immunotherapy and cryoablation is a novel approach, previous studies have shown promising results with similar immunotherapy strategies in cancer treatment.

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.

Where this trial is running

Shanghai, Shanghai Municipality and 2 other locations

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, 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)

Study contacts

• Study coordinator: Ziming Li, Doctor

Conditions Non-small Cell Lung Cancer; Oligo-progression; Toripalimab; Cryoablation