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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

Participants must meet all of the following criteria for enrollment: 1. Age ≥18 years; 2. Histologically-confirmed unresectable Stage III or IV melanoma, unsuitable for local therapy; 3. 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); 4. Participants with BRAF/CKIT/NRAS gene mutations must have progressed after targeted therapy; 5. Intolerant to chemotherapy or refused standard therapy; 6. 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; 7. Life expectancy of at least 3 months; 8. Eastern Cooperative Oncology Group (ECOG) score: 0-1; 9. At least one measurable lesion confirmed according to RECIST 1.1 criteria; 10. Laboratory test results at screening must meet the following requirements: a) 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; 11. 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; 12. Provide written informed consent, and are expected to have good compliance with the study protocol.

Exclusion Criteria:

Participants meeting any of the following will be excluded: 1. 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); 2. Received more than 10 mg of prednisolone or other immunosuppressive therapy within seven days prior to study treatment; 3. Severe allergic reaction to other monoclonal antibodies; 4. 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); 5. Underwent any major surgery requiring general anesthesia within 28 days prior to the first dose; 6. 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; 7. With bone metastasis who received palliative radiotherapy to >5% of the bone marrow area within four weeks prior to study entry; 8. Known allergy to recombinant humanized anti-PD-(L)1 monoclonal antibody drugs, recombinant humanized anti-CTLA-4 monoclonal antibody, and/or their components; 9. Concurrent other malignancies; 10. Concurrent participation in other interventional clinical trials; 11. HIV positive; HCV positive; HBsAg or HBcAb positive with detectable HBV DNA copies (quantitative detection limit of 500 IU/ml); 12. Received live vaccine vaccination within four weeks prior to treatment initiation; 13. Ocular melanoma; 14. 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT07004335
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hebei Medical University Fourth Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Not yet recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

PD-(L)1, CTLA-4, Advanced Melanoma, Iparomlimab, Tuvonralimab, Bevacizumab
Additional Details

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.

Arms & Interventions

Arms

Experimental: Experimental Arm

anti PD-1/CTLA-4 (Iparomlimab/Tuvonralimab) injection and Bevacizumab

Interventions

Drug: - Iparomlimab and Tuvonralimab Injection plus Bevacizumab

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).

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Shijiazhuang, China

Status

Address

The Fourth Hospital of Hebei Medical University

Shijiazhuang, ,

Site Contact

Zhiyu Wang, MD

[email protected]

008631186095810

Stay Informed & Connected