Advanced malignant solid tumor
Conditions
Interventions
Dose Escalation test -1:0.001mg/kg
Dose Escalation test -2:0.003mg/kg
Dose Escalation test -3:0.03mg/kg
Dose Escalation test -4:0.15mg/kg
Dose Escalation test -5:0.5mg/kg
Dose Escalation test -6:1.0mg/kg
Dose escalation test -7:2.0mg/kg
Dose Escalation test -8:3.0mg/kg
Extension Stage:3.0mg/kg
Sponsors
Shanghai Dongfang Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 75 years; 2. Patients with histologically or cytologically confirmed local recurrent or metastatic solid tumors who have failed standard treatment, or have no standard treatment, or are currently not eligible for standard treatment, or cannot tolerate standard treatment; 3. Measurable tumor lesions: According to RECISIT1.1, there is at least one measurable tumor lesion for patients in expansion group; 4 Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 5. Life expectancy of greater than 3 months; 6. Adequate organ function: hematological system (no blood transfusion or hematopoietic stimulator therapy within 14 days) : Absolute neutrophil count (ANC) >= 1.5 x 10^9/L, platelet count (PLT) >= 75x10^9/L, hemoglobin (Hb) >= 90g/L; Hepatic function: total bilirubin (TBIL) 50ml/min by the Cockcroft-Gault formula; Coagulation function: Activated partial thrombin time (APTT) <= 1.5 ULN, international standardized ratio (INR) <= 1.5 ULN; 7. Patients of childbearing potential (male and female) must agree to use reliable contraceptive methods (hormonal or barrier methods or abstinence) with their partners from signing ICF to at least 90 days after the last dose; For women of reproductive potential, blood or urine pregnancy tests must be negative within 7 days before the first dosing; 8. Subjects shall be given informed consent prior to the study and willingly sign the forms.
Exclusion criteria
Exclusion criteria: 1. Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 4 weeks prior to study day1, except for: Nitrourea or mitomycin C used within 6 weeks before the first dose. Oral fluorouracil and molecule targeting drugs administered within 2 weeks before the first dose or 5 half-lives of the drug (whichever is longer); Herbal medicine with anti-tumor indications used within 2 weeks before study day1. 2. Enrolled in other unlisted investigational drug or device study within 4 weeks prior to the first dose. 3. Had major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose, or needed to undergo elective surgery during the study period. 4. Received systemic glucocorticoids (prednisone > 10mg/ day or equivalent drug) or other immunosuppressive therapy within 14 days prior to the first dose; Except for topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids; Short-term use of glucocorticoids for prophylactic treatment (e.g. to prevent contrast agent-induced allergic reactions); 5. Used immunomodulator, including but not limited to thymosin, interleukin-2, interferon, etc. within 14 days prior to the first dose; 6. Live attenuated vaccine administered within 4 weeks prior to the first dose; 7. Prior therapy with 4-1BB agonist; 8. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ transplantation. 9. Adverse reactions from previous antitumor therapy have not yet resolved to CTCAE v5.0 grade 0 or 1 ( alopecia, pigmentation, neurotoxicity, etc.resolved to grade 2 or below, except for that determined by the researchers to be of no safety risk); 10. Patients with clinical symptoms of CNS/meningeal metastases, or other evidences of uncontrolled metastases, are not eligible for inclusion upon the investigator's judgment; 11. Patients with active infection within 1 week prior to study day 1 and currently requiring systemic anti-infective therapy; 12. A history of immunodeficiency, including but not limited to positive HIV test; 13. Positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV); 14. Hepatic hilar lesions or large hepatic tumor lesions (such as > 5cm in length) judged to be at risk of obstruction within 1 month; 15. A history of serious cardiovascular and cerebrovascular diseases, including but not limited to: serious heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, II, III degree atrioventricular conductive block, QTc interval >= 480 ms, etc.; Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months before study day 1; American New York Heart Association (NYHA) >= class II or left ventricular ejection fraction (LVEF) = grade 2; 18. Subjects with uncontrolled third space effusion are not suitable for inclusion according to the judgment of the researchers; 19. Subjects with mental disorders or poor complianc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| blood routine examination;coagulation function;12-Lead electrocardiogram;urine routine test;vital signs;physical examination;adverse events and serious adverse events;blood biochemistry;Pharmacokinetic index: AUC0-last, AUC(0-24), AUC (0-8), Cmax, t1/2, Vd, CL;Immunogenicity index: ADA, Nab;pharmacodynamics index: IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-gama, TNF-alpha;T cell, NK cell, B cell;objective response rate;progression free survival;disease control rate;duration of remission; | — |
Countries
China
Contacts
Public ContactLi jin
Shanghai Oriental Hospital
Outcome results
None listed