Non-small Cell Lung CancerPhase 2NCT06127303
Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC
A Phase 2 study testing Toripalimab and Cryoablation in people with Non-small Cell Lung Cancer, run by Shanghai Chest Hospital at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Toripalimab and Cryoablation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 3 sitesChina
- Study dates
- 2 Apr 2024to 2 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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；
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, 200000
Ziming Li, Doctor, 0086-13764590226, liziming1980@163.com
- Not yet recruiting
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Xi Liang, MD,PHD, +8613501814090, aihuabao312@126.c0m
- Not yet recruiting
Zhongshan Hospital, Fudan University
Shanghai
Yong Zhang, MD,PHD, +8615000229853, zhang.yong@zs-hospital.sh.cn
About this study
Official title: A Single-arm, Phase II Clinical Study of Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC
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
- Being tested
- Toripalimab, Cryoablation
- Keywords
- Oligo-progression, Toripalimab, Cryoablation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called Immunotherapy
Toripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after cryoablation, until occurrence of termination event specified in the protocol.
CryoablationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Toripalimab; Other: Cryoablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (5)
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1.
Measured: 6 months
Disease control rate (DCR)
DCR was defined as the percentage of cases with remission (PR + CR) and stable lesions (SD) after treatment was assessable.
Measured: 6 months
Overall Survival (OS)
OS was defined as the duration from the date of randomization until the date of death from any cause.
Measured: 24 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Frequency table will be used to summarize occurrence of each treatment-emergent AE. Number and classification of participants with treatment-related adverse events as assessed by CTCAE v5.0 were recorded.
Measured: Up to 2 years
Correlation analysis of PD-L1 expression of tumor and ORR
Correlation Analysis of the PD-L1 expression in tumor tissue specimen related with the tumor response.
Measured: Up to 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start2 Apr 2024
- Primary completion2 Apr 2026 (estimated)
- Study completion2 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Chest HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ziming Li, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06127303
- Sponsor's protocol ID
- IS23070
- Status last verified
- Aug 2025
- First submitted
- 7 Nov 2023
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Phase II Clinical Study of Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC
- ClinicalTrials.gov ID
- NCT06127303
- Acronym / sponsor ID
- IS23070
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Oligo-progression, Toripalimab, Cryoablation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Study start
- 2 Apr 2024 (actual)
- Primary completion
- 2 Apr 2026 (estimated)
- Study completion
- 2 Apr 2028 (estimated)
- First posted
- 13 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab Combined with Cryoablation | Experimental | Drug: Toripalimab, Other: CryoablationPatients with oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress would be treated with Toripalimab Combined with Cryoablation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ToripalimabAlso: ImmunotherapyToripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after cryoablation, until occurrence of termination event specified in the protocol. | Drug | Toripalimab Combined with Cryoablation |
| CryoablationThe 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. | Other | Toripalimab Combined with Cryoablation |
Primary outcome
Progression Free Survival (PFS)
Time frame: 6 months
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.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: 6 months
Disease control rate (DCR)
Time frame: 6 months
Overall Survival (OS)
Time frame: 24 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Up to 2 years
Correlation analysis of PD-L1 expression of tumor and ORR
Time frame: Up to 1 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab and Cryoablation in people with Non-small Cell Lung Cancer, run by Shanghai Chest Hospital at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ziming Li, Doctor (0086-13764590226, liziming1980@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2025.