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AzTrials

PD-(L)1Phase 4NCT07004335

Efficacy and Safety of Iparomlimab and Tuvonralimab Injection in Combination With Bevacizumab After Progression on Anti-PD-(L)1 Therapy in Advanced Melanoma: A Prospective, Single-Arm, Exploratory Clinical Study

A Phase 4 study testing Iparomlimab and Tuvonralimab Injection plus Bevacizumab in people with PD-(L)1 and CTLA-4, run by Hebei Medical University Fourth Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Several studies have shown that the combination of Iparomlimab, Tuvonralimab, and Bevacizumab exhibits potent anti-tumor activity and favorable safety in various solid tumors, including liver cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
PD-(L)1, CTLA-4, Advanced Melanoma
What is being tested?
Iparomlimab and Tuvonralimab Injection plus Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChina
Study dates
1 Jul 2025to 31 Jan 2029
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must meet all of the following criteria for enrollment:
  • Age ≥18 years;
  • Histologically-confirmed unresectable Stage III or IV melanoma, unsuitable for local therapy;
  • Confirmed PD according to iRECIST within 12 weeks after receiving the last dose of anti-PD-(L)1 monotherapy or in combination with other treatments (including anti-CTLA-4) for at least two doses. (Up to 25% of participants may have received both anti-CTLA-4 and anti-PD-(L)1 treatment);
  • Participants with BRAF/CKIT/NRAS gene mutations must have progressed after targeted therapy;
  • Intolerant to chemotherapy or refused standard therapy;
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  • Toxicity from the most recent treatment recovered to grade 1 or below (except alopecia); if participants underwent major surgery or radiotherapy >30 Gy, they must have recovered from treatment-related toxicities/complications;
  • Life expectancy of at least 3 months;
  • Eastern Cooperative Oncology Group (ECOG) score: 0-1;
  • At least one measurable lesion confirmed according to RECIST 1.1 criteria;
  • Laboratory test results at screening must meet the following requirements:
  • Hematological tests must meet the following criteria (no blood/blood product transfusion, no correction with G-CSF or other hematopoietic stimulants within 14 days): i. Hemoglobin (Hb) ≥ 90 g/L ii. Neutrophil count (ANC) ≥ 1.5 × 10^9/L iii. Platelet count (PLT) ≥ 100×10^9/L b) Biochemical tests must meet the following criteria: i. Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN) ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 ULN (<5 ULN for participants with liver metastasis) iii. Serum creatinine (Cr) ≤ 1.5 ULN or endogenous creatinine clearance rate > 50ml/min (Cockcroft-Gault formula) iv. Urine routine test results show urine protein (UPRO) < 2+ or 24-hour urine protein quantification <1g;
  • Women of childbearing potential must have taken reliable contraceptive measures, had a negative pregnancy test (serum or urine) within 7 days before enrollment, and agree to use appropriate contraception during the trial and for 6 months after the last administration of the investigational drug. Nursing mothers should discontinue breastfeeding during the whole trial period and for 6 months after the last administration of the investigational drug to avoid the drug affecting the infant through milk. For men, they must agree to use appropriate contraception during the trial and for 120 days after the last administration of the investigational drug or have undergone surgical sterilization;
  • Provide written informed consent, and are expected to have good compliance with the study protocol.

Who cannot join

  • Participants meeting any of the following will be excluded:
  • Any active autoimmune disease or a history of autoimmune disease requiring treatment (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hepatitis, pituitary炎, vasculitis, nephritis, hyperthyroidism; participants with vitiligo; childhood asthma that has completely resolved without any intervention in adulthood can be included; participants with asthma requiring bronchodilators for medical intervention cannot be included);
  • Received more than 10 mg of prednisolone or other immunosuppressive therapy within seven days prior to study treatment;
  • Severe allergic reaction to other monoclonal antibodies;
  • Uncontrolled cardiac clinical symptoms or disease, such as: heart failure of NYHA class 2 or above; unstable angina; myocardial infarction within the past year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; QTc >450 ms (males); QTc >470 ms (females);
  • Underwent any major surgery requiring general anesthesia within 28 days prior to the first dose;
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  • Active infection, unexplained fever ≥38.5°C within seven days prior to medication, or baseline white blood cell count >15×10⁹/L; or suppurative and chronic infections, non-healing wounds;
  • With bone metastasis who received palliative radiotherapy to >5% of the bone marrow area within four weeks prior to study entry;
  • Known allergy to recombinant humanized anti-PD-(L)1 monoclonal antibody drugs, recombinant humanized anti-CTLA-4 monoclonal antibody, and/or their components;
  • Concurrent other malignancies;
  • Concurrent participation in other interventional clinical trials;
  • HIV positive; HCV positive; HBsAg or HBcAb positive with detectable HBV DNA copies (quantitative detection limit of 500 IU/ml);
  • Received live vaccine vaccination within four weeks prior to treatment initiation;
  • Ocular melanoma;
  • With active brain metastasis (previously untreated asymptomatic brain metastasis patients with ≤3 brain lesions and longest diameter <1 cm can be included. Previously treated brain metastasis patients who are clinically stable with no new or enlarged brain metastasis and have not used steroids for ≥14 days prior to study intervention can be included); other severe, acute, or chronic medical or mental disorders or laboratory abnormalities that may increase the risk associated with study participation or may interfere with the interpretation of study results, as judged by the investigator.

Trial locations and contacts

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

Zhiyu Wang, MD contact

008631186095810

drwangzhiyu@hotmail.com

China1 site

  • The Fourth Hospital of Hebei Medical University

    Shijiazhuang

    Zhiyu Wang, MD

Other trials in China

About this study

Several studies have shown that the combination of Iparomlimab, Tuvonralimab, and Bevacizumab exhibits potent anti-tumor activity and favorable safety in various solid tumors, including liver cancer. However, the efficacy and safety of this regimen in melanoma patients with acquired resistance to immunotherapy remain unexplored and require further validation.

This study aims to evaluate the efficacy and safety of the Iparomlimab, Tuvonralimab, and Bevacizumab combination in patients with immune-resistant melanoma. Furthermore, it will analyze and compare treatment responses among different melanoma subtypes to identify optimal treatment strategies for clinical practice.

Read the detailed description

This is a single-center, prospective, single-arm, exploratory clinical trial. Following the signing of informed consent, all participants will undergo screening according to the inclusion and exclusion criteria.It is anticipated that a total of 40 patients will be enrolled. Participants will receive a combination of Iparomlimab/Tuvonralimab injection and Bevacizumab every 3 weeks. Follow-up visits will be scheduled every 6 weeks. The final assessment of the study endpoints will take place at Week 105, while the last evaluation of other adverse events will be conducted at Week 109.

Being tested
Iparomlimab and Tuvonralimab Injection plus Bevacizumab
Keywords
Immunotherapy, Immune Checkpoint Inhibitors
Medical subject headings
Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

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

  • Iparomlimab and Tuvonralimab Injection plus BevacizumabDrug

    The experimental group will receive intravenous infusion of anti PD-1/CTLA-4 (Iparomlimab/Tuvonralimab) Injection (5 mg/kg) and Bevacizumab (dose 7.5mg/kg) once every 3 weeks up to 35 cycles (105 weeks).

Study groups in NCT07004335
Study groupRoleWhat they receive
Experimental ArmExperimentalanti PD-1/CTLA-4 (Iparomlimab/Tuvonralimab) injection and Bevacizumab
Receives: Drug: Iparomlimab and Tuvonralimab Injection plus Bevacizumab

What is being measured

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

  1. Objective Response Rate, ORR

    ORR includes complete response (CR) and partial response (PR) cases. According to RECIST V1.1, the first appearance of PR or CR requires additional imaging to confirm the lesion

    Measured: 105 weeks

Secondary outcomes (3)

  1. Overall Survival Time, OS

    Overall survival (OS) is the time between the participant's first infusion injection and death from any cause.

    Measured: 105 weeks

  2. Progression-free Survival, PFS

    Progression-free survival (PFS) is defined as the time between a participant's first treatment and the first radiographic evaluation of disease progression or death from any cause, whichever comes first.

    Measured: 105 weeks

  3. Duration of Overall Response, DOR

    It was defined as the time from the first documentation of an objective response (CR or PR) to the first documentation of objective disease progression (according to RECIST v1.1 criteria) or death from any cause, whichever occurred first.

    Measured: 105 weeks

Timeline

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

  1. First posted4 Jun 2025
  2. Study start1 Jul 2025 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Jan 2029 (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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07004335
Sponsor's protocol ID
2025045
Status last verified
May 2025
First submitted
27 May 2025
Last updated
4 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Iparomlimab and Tuvonralimab Injection plus Bevacizumab in people with PD-(L)1 and CTLA-4, run by Hebei Medical University Fourth Hospital 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 14 inclusion and 15 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: opening soon, as of the sponsor's last update on 4 Jun 2025. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 Zhiyu Wang, MD (008631186095810, drwangzhiyu@hotmail.com), 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: 105 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07004335.

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 4 Jun 2025.

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