locally advanced unresectable or metastatic melanoma following failure of prior treatment with immune checkpoint inhibitors
Conditions
Interventions
Medication administration group:DNV3 in combination with toripalimab and chemotherapy
Sponsors
Fujian Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Subjects must be fully informed about the study, voluntarily sign the informed consent form, and be willing and able to comply with the study procedures. 2.Subjects must be between 18 and 75 years old. 3.Histologically confirmed locally advanced unresectable or metastatic melanoma, including three subtypes: acral, mucosal, or non-acral cutaneous. 4.Subjects must have previously received at least one line of systemic antitumor therapy, including immune checkpoint inhibitors. For subjects with a BRAF V600 mutation, prior treatment with both BRAF inhibitors and immune checkpoint inhibitors is required. 5.The BRAF mutation status of the subject must be known. If unknown, BRAF mutation testing must be completed before formal enrollment. 6.Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7.Subjects must have an expected survival of = 3 months. 8.At least one measurable lesion according to RECIST v1.1 criteria, and the target lesion must not have undergone prior radiation therapy. 9.Before the first investigational treatment administration, prior treatments must be completed within the following timeframes: Systemic Antitumor Therapy: At least five half-lives or 4 weeks (whichever is shorter) since the last systemic antitumor therapy. Local Radiotherapy: At least 2 weeks since the last radiotherapy, and any acute toxicities from prior radiotherapy must have resolved to Grade 1 or lower. 10. Adequate organ function, as defined by the following laboratory test results (no blood transfusions, growth factors, albumin, or other corrective medications allowed within 14 days before the laboratory tests): Hematologic Function (no transfusions or hematopoietic stimulators in the past 14 days): Absolute Neutrophil Count (ANC) = 1.5 × 10^9/L Platelets (PLT) = 100 × 10^9/L Hemoglobin (Hb) = 90 g/L Liver Function: Total Bilirubin (TBIL) = 1.5 × upper limit of normal (ULN) (= 3.0 × ULN for subjects with Gilbert's syndrome or liver metastases/liver cancer) Alanine Aminotransferase (ALT) = 2.5 × ULN (= 5.0 × ULN for subjects with liver metastases) Aspartate Aminotransferase (AST) = 2.5 × ULN (= 5.0 × ULN for subjects with liver metastases) Albumin = 3.0 g/dL Renal Function: Serum Creatinine = 1.0 × ULN; or Creatinine Clearance (Ccr) = 60 mL/min (calculated using the Cockcroft-Gault formula, only applicable if creatinine > 1.0 × ULN) Urine protein = 2+ Coagulation: Activated Partial Thromboplastin Time (aPTT) = 1.5 × ULN International Normalized Ratio (INR) and Prothrombin Time (PT) = 1.5 × ULN 11.Female subjects must provide evidence of postmenopausal status, or if premenopausal, a negative serum pregnancy test result. Fertile subjects (both male and female) must agree to use effective contraception (e.g., hormonal or barrier methods, or abstinence) during the study and for at least 90 days after the last dose of the investigational product.
Exclusion criteria
Exclusion criteria: 1.Subjects who previously discontinued treatment due to severe and/or life-threatening immune-related toxicity from prior immunotherapy. 2.Subjects with unresolved adverse events from prior antitumor treatments that have not recovered to = Grade 1 per NCI-CTCAE v5.0 at the time of enrollment (excluding alopecia or investigator-determined tolerable events related to antitumor treatment). 3.Subjects who have participated in another clinical trial and used investigational drugs within 4 weeks prior to the first dose of study drug. 4.Subjects who have taken herbal decoctions or traditional Chinese medicine preparations with antitumor indications within 2 weeks prior to the first dose of study drug. 5.Subjects who have received systemic corticosteroids (prednisone >10 mg/day or an equivalent dose of another corticosteroid) or other immunosuppressive agents within 7 days prior to the first dose of study drug. 6.Subjects who have undergone major organ surgery (excluding biopsy or fully recovered minimally invasive surgery) or have experienced significant trauma within 4 weeks prior to the first dose of study drug, or who are scheduled for elective surgery during the study. 7.Subjects with a history of other primary malignancies within the past 5 years, with the exception of patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has been treated with curative intent and without recurrence in the 5 years prior to screening. 8.Subjects with severe medical conditions, including: Severe cardiac disease, such as pulmonary hypertension, unstable angina, myocardial infarction within 6 months prior to the first dose of study drug, coronary artery bypass grafting, or coronary artery stenting, NYHA Class 3-4 heart failure, clinically significant valvular disease, left ventricular ejection fraction (LVEF) 480 milliseconds. Cerebrovascular disease, such as a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to the first dose of study drug. Uncontrolled diabetes, uncontrolled hypertension (defined as systolic blood pressure =150 mmHg and/or diastolic blood pressure =100 mmHg after treatment), active gastrointestinal ulcers, or active bleeding. 9.Subjects with uncontrolled pleural effusion, pericardial effusion, or symptomatic ascites within 6 months prior to the first dose of study drug that cannot be controlled with appropriate interventions. 10.Subjects with central nervous system (CNS) metastases, except for stable brain metastases that have been treated by radiotherapy or surgery and meet the following criteria: Seizure-free status for more than 12 weeks with or without antiepileptic medication. No need for corticosteroids. Two consecutive MRI scans (at least 4 weeks apart) show radiological stability. No symptoms and clinical stability for more than 1 month after treatment. 11.Subjects with current or previous non-infectious interstitial lung disease (ILD), including but not limited to pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonitis, or severely impaired lung function. 12.Subjects with active autoimmune diseases at screening, including but not limited to immune-related myocarditis, immune-related pneumonitis, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflamma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR (objective response rate); | — |
Secondary
| Measure | Time frame |
|---|---|
| DOR (duration of response);PFS(progression free survival);OS(overall survival);incidence of adverse events;Laboratory aberrations;The severity of adverse events;PK(pharmacokinetics);ADA(Anti-drug antibody); | — |
Countries
China
Contacts
Public ContactChen Yu
Fujian Cancer Hospital
Outcome results
None listed