Rare neoplasm of skin
Conditions
Interventions
Skin angiosarcoma:DNV3 and toripalimab injection for injection
Squamous cell carcinoma of skin:DNV3 and toripalimab injection for injection
Malignant melanoma of skin:DNV3 and toripalimab injection for injection
Sweat gland ductal carcinoma of skin:DNV3 and toripalimab injection for injection
Leiomyosarcoma of skin:DNV3 and toripalimab injection for injection
Merkel cell carcinoma:DNV3 and toripalimab injection for injection
Other types of rare skin neoplasm:DNV3 and toripalimab injection for injection
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible. 1. Understand the trial procedures and contents, and voluntarily sign the written informed consent form. 2. Age >= 18 years at the time of signing the informed consent form, male or female. 3. (Applicable to Part A dose escalation phase) Subjects with recurrent/metastatic rare skin neoplasm that cannot be treated surgically and have failed or cannot tolerate systemic standard treatment or currently have no effective standard treatment (preferably Part B specific tumor types). 4. (Applicable to Part B dose expansion phase) Subjects with histologically confirmed rare skin neoplasm that is not amenable to surgical treatment and has failed or is intolerant to systemic standard treatment or currently has no effective standard treatment.The target tumor types include: skin angiosarcoma, skin squamous cell carcinoma (SCC), skin malignant melanoma, skin sweat gland ductal carcinoma, skin leiomyosarcoma, Merkel cell carcinoma, and other rare skin neoplasm. 5. Consent to provide archival neoplasm tissue specimen or fresh tissue sample (optional). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Expected survival >= 3 months. 8. There must be at least one measurable (and must be outside the CNS) neoplasm. 9. At least 3 weeks after the last administration of systemic chemotherapy before the first study medication (if the chemotherapy drugs are nitrosoureas and mitomycin C, at least 6 weeks before the last chemotherapy; 2 weeks after the elution of oral fluorouracil drugs); Monoclonal antibody drugs (including antibodies/drugs targeting immune checkpoints such as programmed death protein (PD-1), programmed death protein ligand (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), etc.) should be administered at least 3 weeks after the last dose of treatment; At least 2 weeks after the last administration of small molecule targeted drug therapy, and at least 3 weeks after the last administration of antibody conjugated drug (ADC) therapy; At least 2 weeks after the last administration of traditional Chinese patent medicines and simple preparations with anti-tumor indications. 10. Prior to the first study medication, radiation therapy has been completed for at least 2 weeks, and the acute toxic reactions caused by previous radiotherapy have recovered to = 1.0 x 10^9/L; Platelets (PLT) >= 90 x 10^9/L; Haemoglobin (Hb) >= 90 g/L; Hepatic function Bilirubin total (TBIL) <= 1.5 x upper limit of normal (ULN) (<= 3.0 x ULN for subjects with Gilbert's syndrome or metastases to liver/hepatic cancer); Alanine aminotransferase (ALT) <= 2.5 × ULN; Subjects with Metastases to liver/hepatic cancer: <= 5.0 x ULN; Aspartate aminotransferase (AST) <= 2.5 × ULN; Subjects with Meta
Exclusion criteria
Exclusion criteria: Subjects will be ineligible if any of the following conditions occur. 1. Prior antibody/drug therapy targeting the LAG-3 immunization checkpoint. 2. Previous CAR-T cell therapy. 3. Use of other investigational study drugs within 3 weeks before the first study drug administration. 4. Prior interruption of treatment due to severe and/or life-threatening anti-PD-1 or anti-PD-L1 antibody-related toxicity. 5. Patients with other neoplasm malignant within the past 5 years, except for those with cured skin basal cell carcinoma, superficial bladder cancer, carcinoma in situ of breast, cervix carcinoma in situ and cervix carcinoma in situ, and papillary thyroid cancer. 6. Symptomatic or active progression of central nervous system (CNS) metastases/primary Only subjects with CNS lesions and who are therapy naive and asymptomatic will be included in the study if they meet all of the following criteria and are judged by the investigator to be: • The subject had no history of haemorrhage intracranial or spinal cord haemorrhage. • Subjects did not receive stereotactic body radiotherapy or whole brain radiotherapy within 4 weeks before the first study medication. • Subjects were not on a continuous regimen of corticosteroids while on CNS disease treatment.Stable doses of anticonvulsant medications are allowed. 7. Have an active autoimmune disorder or a history of autoimmune disorder that may flare or be associated with symptoms and require treatment with systemic steroids or immunosuppressants. Note: Subjects with vitiligo or asthma/hypersensitivity that has been cured may be considered for enrollment.Intermittent use of bronchodilators or topical steroid injection, type I diabetes mellitus, need for hormone replacement therapy, and stable disease with thyroid function decreased should not be excluded. 8. Concurrent conditions that require treatment with immunosuppressive drugs, or that require systemic therapy with doses having immunosuppressive activity (e.g., prednisone > 10 mg/day or equivalent dose of other immunosuppressive agents); in the absence of active autoimmune disorder, Inhalation or topical use of corticosteroids, or adrenal replacement therapy with a dose of 480milliseconds], cerebrovascular disease [history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA) within 6 months prior to first study drug administration], uncontrolled diabetes mellitus, uncontrolled hypertension (blood pressure systolic >= 150 mmHg and/or blood pressure diastolic >= 100 mmHg), active gastrointestinal ulcer, active haemorrhage, etc. 10. Refractory ascites that cannot be controlled by appropriate intervention and pleural effusion or pericardial effusion that cannot be controlled by appropriate intervention or requires >= 1 drainage per month. 11. Now or pre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability ;Objective response rate (ORR) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Cmax;Tmax;t1/2;immunogenicity;duration of remission;disease control rate;progression free survival;Overall survival; | — |
Countries
China
Contacts
Public ContactMeiyu Fang
Zhejiang Cancer Hospital
Outcome results
None listed