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

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

Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC (NCT06127303) is a Phase 2 interventional studying Non-small Cell Lung Cancer, sponsored by Shanghai Chest Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Non-small Cell Lung Cancer and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 54 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Non-small Cell Lung Cancer subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Voluntary participation and written willing to sign a consent form; - diagnosed by tissue sample (biopsy-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. Who Should NOT Join This Trial: - cytologically or diagnosed by tissue sample (biopsy-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; ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DRUG

Toripalimab

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

OTHER

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.

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

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

Shanghai, China

Zhongshan Hospital, Fudan University

Shanghai, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06127303), the sponsor (Shanghai Chest Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06127303 clinical trial studying?

Who can participate in NCT06127303?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06127303?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06127303. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06127303. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.