Patients with unresectable or metastatic stage III or IV acral melanoma
Conditions
Interventions
Trial Group:Epatolitorovarelimab 5mg/kg Q3W + Carboplatin AUC 5 or Cisplatin 75mg/m2 Q3W + Bevacizumab 5mg/kg D1 Q3W, one treatment cycle every 21 days for 4 cycles
after 2 cycles, large fractionation radiotherapy (8Gy/5F) for residual lesions, followed by maintenance therapy.
Sponsors
The affiliated hospital of southwest medical university
Eligibility
Sex/Gender
All
Age
18 Years to 78 Years
Inclusion criteria
Inclusion criteria: 1.Male or female, aged 18–78 years (inclusive); 2.Voluntarily sign a written informed consent form; 3.Patients with histologically confirmed unresectable or metastatic stage III or IV acral melanoma (primary site: palms, soles, or subungual region); 4.No prior systemic chemotherapy, targeted therapy, or immunotherapy for advanced melanoma; 5.At least one measurable tumor lesion according to the RECIST v1.1 criteria. 6.ECOG PS 0 or 1; 7.Expected survival time>=3 months; 8. Adequate major organ function: (1) Hematological function (no supportive therapy with any blood components or cell growth factors within 7 days prior to the start of study treatment):1)Absolute neutrophil count (ANC) >=1.5 × 10^9/L (1,500/mm^3).2)Platelet count >=100 × 10^9/L (100,000/mm^3).3)Hemoglobin >= 90 g/L.(2) Renal function:1)Calculated creatinine clearance (CrCl) >= 50 mL/min, where CrCl is determined using the Cockcroft-Gault formula.2)Urinary protein < 2+ on dipstick test, or 24-hour urinary protein quantification < 1.0 g.(3) Hepatic function:1)Serum total bilirubin (TBil) <=1.5 × upper limit of normal (ULN).2)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × ULN.3)For subjects with hepatic metastases: Serum total bilirubin (TBil) <= 3 × ULN; AST and ALT <=5 × ULN.(4) Coagulation function:1)International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) <= 1.5 × ULN. 9.Female subjects of childbearing potential must undergo a serum pregnancy test within 3 days prior to the first dose, with a negative result. If a female subject of childbearing potential engages in sexual activity with an unsterilized male partner, she must adopt an acceptable contraceptive method starting from screening and agree to continue using this contraceptive method for 6 months after the last dose of the study drug; the decision to discontinue contraception after this time point should be discussed with the investigator; 10.The subject is willing and able to comply with the visits, treatment plan, laboratory tests specified in the schedule, as well as other requirements of the study.
Exclusion criteria
Exclusion criteria: 1.Participation in experimental drug treatment or use of experimental medical devices within 4 weeks prior to the first administration of iparomlimab and tuvonralimab; 2.History of other active malignant tumors within 3 years prior to enrollment. Exceptions include locally curable malignant tumors (demonstrated as cured), such as basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, endometrial carcinoma, cervical carcinoma in situ, or breast carcinoma in situ; 3.Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional study (defined as the time from the first dose of the current study being at least 4 weeks or 5 half-lives of the previous study drug, whichever is longer); 4.reatment, or autoimmune diseases judged by the investigator to have potential for recurrence or requiring planned treatment; exceptions include: dermatological conditions not requiring systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema); hypothyroidism caused by autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; well-controlled type 1 diabetes mellitus; subjects with childhood asthma that has been completely resolved and requires no intervention in adulthood; diseases judged by the investigator to not recur without external triggers.; 5.Complicated with active inflammatory bowel disease requiring clinical treatment (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea); 6.Subjects requiring systemic treatment with corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days after taking the study drug. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal replacement doses >10 mg/day prednisone equivalent are permitted. Subjects are allowed to use topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids (with minimal systemic absorption). Physiological replacement doses of systemic corticosteroids are permitted, even if >10 mg/day prednisone equivalent. Short-term use of corticosteroids for prophylaxis (e.g., contrast medium allergy) or treatment of non-autoimmune diseases (e.g., delayed-type hypersensitivity reactions caused by contact allergens) is permitted; 7.Exclude patients with BRAF V600E mutation currently receiving targeted therapy (dabrafenib + trametinib, vemurafenib + cobimetinib, selumetinib); 8.Previous receipt of anti-angiogenic inhibitors (e.g., bevacizumab, anlotinib, pazopanib, regorafenib, etc.), immune checkpoint inhibitors (e.g., anti-PD-1 antibodies, anti-PD-L1 antibodies, etc.), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40, etc.), immune cell therapy, or any other treatments targeting tumor immune mechanisms; 9.Known history of positive human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) test; 10.Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 11.Known active interstitial lung disease or history thereof; 12.Subjects with necrotic lesions detected within 4 weeks prior to enrollment, which the investigator judges to have a high risk of massive bleeding; 13.Severe infection occurring within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; 14.Known active tub
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival,PFS;Disease Control Rate,DCR;Overall Survival,OS;Duration of Response,DOR;Security;Time to Response, TTR; | — |
Countries
China
Contacts
Public ContactLin Sheng
The affiliated hospital of southwest medical university
Outcome results
None listed