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Melanoma (Skin) Stage IVPhase 2Cryo-IA-CheckNCT07847359

Cryoablation Combined With Hepatic Arterial Infusion of Iparomlimab and Tuvonralimab (QL1706), Intravenous Dacarbazine, and Oral Lenvatinib in Patients With Liver Metastases From Malignant Melanoma: a Single-arm, Phase II, Prospective Trial

A Phase 2 study testing Cryoablation, Iparomlimab and Tuvonralimab and Dacarbazine in people with Melanoma (Skin) Stage IV, run by Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

To explore the efficacy and safety of cryoablation combined with hepatic arterial infusion of iparomlimab and tuvonralimab, intravenous dacarbazine, and oral lenvatinib in patients with liver metastases from malignant melanoma. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Melanoma (Skin) Stage IV
What is being tested?
Cryoablation, Iparomlimab and Tuvonralimab and Dacarbazine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteChina
Study dates
1 Oct 2026to 31 Dec 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

  • Age 18-70 years;
  • Patients with pathologically confirmed metastatic malignant melanoma after failure of standard treatment;
  • Presence of liver metastases, with at least one lesion assessed as suitable for cryoablation;
  • The largest diameter of each intrahepatic metastatic lesion < 5 cm;
  • At least one target lesion suitable for efficacy assessment according to RECIST 1.1 (when no appropriate extrahepatic target lesion is available, a non-ablated intrahepatic lesion may serve as the observation lesion);
  • ECOG performance status score of 0;
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  • No history of autoimmune disease;
  • Life expectancy of more than 3 months;
  • Laboratory test results meeting the following criteria:
  • Neutrophil count >= 1.8 × 10⁹/L;
  • White blood cell count >= 3.0 × 10⁹/L;
  • Platelet count >= 100 × 10⁹/L; Hemoglobin >= 90 g/L;
  • Serum ALT and AST <= 2.5 × the upper limit of normal (ULN);
  • Serum creatinine <= 1.5 × ULN;
  • INR < 1.3 or prothrombin time < ULN + 2 seconds;
  • Albumin >= 35 g/L;
  • Total bilirubin <= 1.0 × ULN.

Who cannot join

  • Liver metastases previously treated with radiotherapy, microwave ablation, radiofrequency ablation, or irreversible electroporation;
  • ECOG performance status score >= 2;
  • Child-Pugh score >= 7; decompensated liver function, such as massive ascites, gastric fundal or esophageal varices with upper gastrointestinal bleeding within the previous year, hepatic encephalopathy, or bilirubin encephalopathy;
  • Known central nervous system metastases that are clinically unstable, or acute meningitis (except patients with central nervous system metastases who have received treatment and are clinically stable).
  • Clinical stability requires all of the following:
  • no new brain lesions and no enlargement of existing lesions, confirmed by MRI;
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  • no glucocorticoid treatment for at least 2 weeks;
  • no new neurological symptoms, and previous neurological symptoms have returned to normal.
  • Previous treatment with immune checkpoint inhibitors complicated by grade 3 or higher immune-related adverse events;
  • Pregnant or breastfeeding women;
  • History of HIV infection;
  • History of another malignancy within 5 years (excluding early-stage basal cell carcinoma, carcinoma in situ of the cervix, and papillary thyroid carcinoma);
  • Any of the following within 12 months before study initiation: myocardial infarction, severe or unstable angina, congestive heart failure, cerebrovascular accident, or pulmonary embolism;
  • Severe hepatic or renal impairment; uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, or acute pulmonary disease; poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 90 mmHg); clinically significant cardiovascular or cerebrovascular disease, such as cerebrovascular accident or myocardial infarction within 6 months, unstable angina, NYHA class II or higher congestive heart failure, severe arrhythmia not controlled by medication, clinically significant electrocardiographic abnormalities on three consecutive recordings obtained at least 5 minutes apart, psychiatric disorders, or drug abuse; or any condition that the investigator considers likely to increase risk to the subject or interfere with study results;
  • History of organ transplantation;
  • Other severe acute or chronic physical or psychiatric illnesses, or laboratory abnormalities, that may increase study-related risk or interfere with interpretation of results and make the patient unsuitable for enrollment;
  • Uncontrolled concurrent diseases or infectious diseases. Patients with active hepatitis B must receive antiviral therapy to achieve HBV DNA < 500 copies/mL and remain stable for at least 2 weeks before the investigator assesses eligibility, and must continue antiviral therapy throughout the study after enrollment;
  • History of severe adverse reactions to contrast agents;
  • Any active autoimmune disease, or a history of autoimmune disease judged by the investigator to make the patient unsuitable for this study, including but not limited to systemic lupus erythematosus, immune-related neuropathy, multiple sclerosis, Guillain-Barre syndrome, myasthenia gravis, connective tissue diseases, and inflammatory bowel disease including Crohn's disease and ulcerative colitis;
  • Previous treatment with lenvatinib or other multi-target tyrosine kinase inhibitors;
  • Previous systemic chemotherapy containing dacarbazine or temozolomide complicated by grade 3 or higher myelosuppression or hepatotoxicity during treatment;
  • Total intrahepatic lesion volume assessed by the investigator as exceeding 50% of the total liver volume;
  • Use of therapeutic anticoagulants (such as warfarin, direct oral anticoagulants, or low-molecular-weight heparin) or dual antiplatelet therapy (such as aspirin combined with clopidogrel) within 7 days before enrollment, if the medications cannot be safely discontinued and bridged before cryoablation and arterial infusion.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lujun Shen, M.D. contact

+86-13560365452

shenlj@sysucc.org.cn

China1 site, 1 recruiting
  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510080

    Lujun Shen, M.D., +86-13560365452, shenlj@sysucc.org.cn

    Letao Lin, M.D., linlt@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: The Efficacy and Safety of Cryoablation Combined With Hepatic Arterial Infusion of Iparomlimab and Tuvonralimab (QL1706), Intravenous Dacarbazine, and Oral Lenvatinib in Patients With Liver Metastases From Malignant Melanoma: a Single-arm, Phase II, Prospective Trial (Cryo-IA-Check-002)

To explore the efficacy and safety of cryoablation combined with hepatic arterial infusion of iparomlimab and tuvonralimab, intravenous dacarbazine, and oral lenvatinib in patients with liver metastases from malignant melanoma.

Read the detailed description

Cryoablation combined with PD-1 blockade has shown encouraging efficacy in melanoma patients with liver metastases, but the response rate remains unsatisfactory and the prognosis is still poor. Our previous CryoCheck-001 study of cryoablation plus sintilimab yielded a response rate of less than 30%. Iparomlimab and tuvonralimab (QL1706) is a novel dual PD-1/CTLA-4 combination antibody with a favorable safety profile, and hepatic arterial infusion of immune checkpoint inhibitors has been confirmed to be effective and safe in melanoma liver metastases. Moreover, adding dacarbazine and lenvatinib may further enhance the efficacy of cryoablation combined with immunotherapy. Herein, we aimed to evaluate the efficacy and safety of cryoablation combined with hepatic arterial infusion of QL1706, intravenous dacarbazine, and oral lenvatinib in patients with liver metastases from malignant melanoma. This is a single-arm, phase II, prospective trial using a Simon two-stage design. Patients receive 1-4 cycles of quadruple therapy (cryoablation plus hepatic arterial infusion of QL1706, intravenous dacarbazine, and oral lenvatinib), followed by maintenance with intravenous QL1706, dacarbazine, and oral lenvatinib until disease progression or intolerable toxicity. The primary endpoint is ORR; secondary endpoints include PFS, OS, and treatment-related adverse events.

Being tested
Cryoablation, Iparomlimab and Tuvonralimab, Dacarbazine, Lenvatinib
Keywords
Cryoablation, hepatic arterial infusion, iparomlimab and tuvonralimab, QL1706, dacarbazine, lenvatinib, liver metastasis, melanoma
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CryoablationProcedure or surgery

    Cryoablation is performed using the Hygea Co-ablation System (Hygea Medical Technology Co. Ltd, Beijing, China), a combined cryoablation and hyperthermic ablation device. Under CT guidance and local anesthesia with 2% lidocaine, one to five intrahepatic lesions with a maximum diameter <5 cm are ablated per session. Each ablation consists of two 10-minute freeze cycles, with a passive thaw between cycles. Technical success is defined as ice-ball extension of at least 0.5 cm beyond the tumor margin. Cryoablation is mandatory in the first cycle and may be repeated in subsequent cycles at the discretion of the investigator, for a maximum of four sessions within 3 months.

  • Iparomlimab and TuvonralimabDrug

    Iparomlimab and tuvonralimab (QL1706; Qilu Pharmaceutical Co., Ltd., Jinan, China) is a dual PD-1/CTLA-4 combination antibody. During the combination phase, QL1706 is administered by hepatic arterial infusion. The catheter tip is positioned in the tumor-feeding artery, proper hepatic artery, or left/right hepatic artery based on intra-hepatic tumor location, and correct positioning is confirmed by repeat angiography. QL1706 7.5 mg/kg diluted in 100 mL of 0.9% normal saline is then infused at a constant rate over 2 hours. Hepatic arterial infusion is given every 3 weeks for a maximum of 4 cycles within 3 months, and if combined with cryoablation, it is administered 7-14 days after ablation. During the maintenance phase, QL1706 is administered intravenously at the same dose every 3 weeks until disease progression or intolerable toxicity. Dose reduction of QL1706 is not permitted.

  • DacarbazineDrug

    Dacarbazine is administered intravenously as a 2-day regimen at a total dose of 850-1000 mg/m², divided over 2 consecutive days, every 3-4 weeks. During the combination phase, dacarbazine is administered intravenously on the day immediately following hepatic arterial infusion of QL1706 (i.e., day 1 after infusion). During the maintenance phase, dacarbazine is continued intravenously at the same dose and schedule until disease progression, intolerable toxicity, or discontinuation after 2 years of maintenance in patients without disease progression.

  • LenvatinibDrug

    Lenvatinib is administered orally at a starting dose of 8 mg once daily. During the combination phase, lenvatinib is started on day 3 after hepatic arterial infusion of QL1706 and catheter removal. During the maintenance phase, lenvatinib is continued orally at the same dose until disease progression or intolerable toxicity, and is continued beyond 2 years after discontinuation of immunotherapy and chemotherapy in patients without disease progression.

Study groups in NCT07847359
Study groupRoleWhat they receive
Interventional ArmExperimentalSingle-arm, open-label, phase II trial. Patients receive quadruple therapy for 1-4 cycles (3-4 weeks per cycle): (1) cryoablation of intrahepatic lesions; (2) hepatic arterial infusion of iparomlimab and tuvonralimab (QL1706) 7.5 mg/kg over 2 hours, 7-14 days after ablation; (3) intravenous dacarbazine 850-1000 mg/m² divided over 2 days; (4) oral lenvatinib 8 mg once daily. After completing the combination phase, patients enter maintenance with intravenous QL1706, dacarbazine, and oral lenvatinib until disease progression or intolerable toxicity. If oligoprogression occurs in the liver, radical radiotherapy to progressing intrahepatic lesions is permitted while maintenance continues.
Receives: Procedure: Cryoablation; Drug: Iparomlimab and Tuvonralimab; Drug: Dacarbazine; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of patients whose best overall response is complete response (CR) or partial response (PR) according to RECIST v1.1, assessed by the investigator. Response evaluation is performed exclusively on pre-specified target lesions that are not subjected to cryoablation. For patients with both intrahepatic and extrahepatic metastases, extrahepatic target lesions are preferentially selected whenever feasible; for patients with intrahepatic lesions only, at least one measurable intrahepatic lesion is deliberately spared from ablation and serves as the target lesion for response assessment. Patients with a first documented CR or PR must have the response confirmed by repeat assessment at least 4 weeks later or at the next scheduled time point.

    Measured: From the initiation of study treatment until disease progression, death, or end of study, assessed up to 48 months.

Secondary outcomes (7)
  1. Progression-Free Survival (PFS)

    PFS is defined as the time from initiation of study treatment to the first documented disease progression on non-ablated target lesions per RECIST v1.1, as assessed by the investigator, or death from any cause, whichever occurs first.

    Measured: From initiation of study treatment to the first documented radiographic disease progression per RECIST v1.1, as assessed by the investigator, or death from any cause, whichever occurs first, assessed up to 48 months.

  2. Overall Survival (OS)

    OS is defined as the time from initiation of study treatment to death from any cause. Patients still alive at the time of analysis are censored at the date of last follow-up. Patients lost to follow-up are censored at the date of last confirmed survival.

    Measured: From the initiation of study treatment to death from any cause, assessed up to 48 months.

  3. 6-Month Progression-Free Survival Rate

    The 6-month PFS rate is defined as the proportion of patients who are alive and free of disease progression on non-ablated target lesions per RECIST v1.1 at 6 months after initiation of study treatment, as assessed by the investigator.

    Measured: 6 months after initiation of study treatment.

  4. Treatment-Related Adverse Events (TRAEs)

    TRAEs are defined as adverse events judged by the investigator to be related to any component of the study treatment (cryoablation, hepatic arterial infusion of QL1706, intravenous dacarbazine, or oral lenvatinib). Adverse events are graded according to NCI-CTCAE v5.0, and the incidence, severity, and type of TRAEs and serious adverse events (SAEs) are recorded.

    Measured: From first dose until 30 days after the last dose of study treatment

  5. Disease Control Rate (DCR)

    DCR is defined as the proportion of patients whose best overall response is complete response (CR), partial response (PR), or stable disease (SD) lasting at least 6 weeks according to RECIST v1.1, as assessed by the investigator. Tumor response is assessed on all target lesions, but only non-ablated target lesions are used to determine the best overall response.

    Measured: From the initiation of study treatment until disease progression, death, or end of study, assessed up to 48 months.

  6. Duration of Response (DoR)

    DoR is defined as the time from the first documented objective response (CR or PR) on non-ablated target lesions to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first, as assessed by the investigator.

    Measured: From the first documented objective response (CR or PR) to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first, assessed up to 48 months.

  7. Time to Progression (TTP)

    TTP is defined as the time from initiation of study treatment to the first documented disease progression on non-ablated target lesions per RECIST v1.1, as assessed by the investigator. Deaths before documented progression are not counted as events for TTP.

    Measured: From the initiation of study treatment to the first documented disease progression per RECIST v1.1, as assessed by the investigator, assessed up to 48 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2026
  2. Study start1 Oct 2026 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07847359
Sponsor's protocol ID
B2026-373-01
Acronym
Cryo-IA-Check
Status last verified
Sep 2026
First submitted
22 Sep 2026
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data will not be shared because the informed consent does not explicitly permit data sharing with other researchers, and patient privacy and institutional data ownership policies apply. Only summary results will be published.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cryoablation, Iparomlimab and Tuvonralimab and Dacarbazine in people with Melanoma (Skin) Stage IV, run by Sun Yat-sen University at 1 site 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 17 inclusion and 23 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 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 Lujun Shen, M.D. (+86-13560365452, shenlj@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From the initiation of study treatment until disease progression, death, or end of study, assessed up to 48 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 29 Sep 2026.

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