Advanced Malignant Solid Tumor or Non-Hodgkin's Lymphoma
Conditions
Interventions
Experimental group1:DF003 0.01mg/kg
Experimental group2:DF003 0.06mg/kg
Experimental group3:DF003 0.3mg/kg
Experimental group4:DF003 1mg/kg
Experimental group5:DF003 3mg/kg
Experimental group6:DF003 6mg/kg
Experimental group7:DF003 10mg/kg
Experimental group8:DF003 15mg/kg
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Be able to understand and voluntarily sign the informed consent; 2. When signing informed consent, the age is >= 18 years old, and the gender is not limited; 3. Advanced malignant solid tumors or non-Hodgkin lymphomas diagnosed by histology or cytology who have failed standard treatment (PD or intolerance) and currently have no standard treatment available. Advanced malignant solid tumors may include, but are not limited to, colorectal cancer, non-small cell lung cancer, renal cell carcinoma, pancreatic cancer, head and neck squamous cell carcinoma, melanoma, etc.; 4. According to RECIST v1.1 criteria or Lugano lymphoma response evaluation criteria (Cheson2014), subjects must have at least one extracranial lesion for efficacy evaluation. The dose escalation phase includes measurable lesions and non-measurable lesions. The number of subjects with all unmeasurable lesions should not exceed 1/3 of the total number of patients enrolled, and in the dose expansion phase, all subjects should have at least one measurable lesion; 5. ECOG physical condition score of 0 or 1; 6. The expected survival period of the subjects is not less than 3 months; 7. Have adequate organ function: (1) Bone marrow function: no blood transfusion or colony-stimulating factor therapy within 14 days before screening: ANC>=1.5x10^9/L (>=1,500/µL), PLT>=90x10^9/L (>=90,000/µL) µL) and HGB > 9.0 g/dL (> 5.6 mmol/L); (2) Renal function: serum creatinine= 60 mL/min (when creatinine>2xULN) (Cockcroft-Gault formula); (3) Liver function: serum total bilirubin 50%, or New York Heart Association (NYHA) heart failure class < II. 8. Any toxicity caused by previous treatment returned to baseline or <= grade 1 (CTCAE v.5.0), except for AEs that did not constitute a safety risk as judged by the investigator; 9. Negative serum or urine pregnancy test (for women of childbearing potential) at screening. Any male or female patient of childbearing potential agrees to use a contraceptive method with an annual failure rate of <1% for the entire duration of the trial and for 90 days after the last study dose (contraceptive methods with an annual failure rate of < 1% include bilateral tubal ligation, male sterilization , Proper use of ovulation-inhibiting hormonal contraceptives, hormone-releasing IUDs, and copper-containing IUDs or condoms) contraception. According to the investigator's judgment, a patient is fertile if he/she is biologically fertile and has a normal sexual life. Infertile female subjects must meet at least one of the following criteria: (1) Postmenopausal state, defined as follows: Absence of menstruation for at least 12 consecutive months in the absence of other pathological or physiological causes; (2) Hysterectomy and/or bilateral oophorectomy has been performed; (3) Medically proven ovarian failure. 10. Willing and able to maintain good communication with investigators and comply with all evaluations and procedures required in the study visit, treatment plan and study protocol.
Exclusion criteria
Exclusion criteria: 1. Subjects with symptomatic brain metastases requiring steroid therapy. Subjects previously diagnosed with brain metastases, if they have completed treatment before screening and have recovered from acute adverse reactions caused by radiotherapy or surgery, have stopped corticosteroid treatment for brain metastases for at least 28 days, and are currently neurologically stable. Eligibility to participate in this study; 2. Those who have received allogeneic hematopoietic stem cell transplantation in the past; Previous treatment with a compound that targets the same mechanism of action of CD137; 3. Patients who need to receive systemic glucocorticoids (>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days before the first dose or during the study period; the following conditions are allowed to enroll: (1) Subjects are allowed to use topical or inhaled glucocorticoids. (2) Allow short-term ( 450 ms, female: QTc > 470 ms (calculated as the average of three repeat readings, approximately 1 min apart, and no history of torsades de pointes or symptomatic QTc abnormalities), symptomatic congestive heart failure, myocardial infarction, and/or pulmonary hypertension , life-threatening ventricular arrhythmia, stroke and uncontrolled severe seizures undergoing maintenance therapy; 14. Other active malignant tumors (excluding basal cell or squamous cell skin cancer or any other carcinoma in situ currently in complete remission) wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limited Toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;the preliminary antitumor activity;Immunogenicity; | — |
Countries
China
Contacts
Public ContactShi Yuankai
Cancer Hospital of Chinese Academy of Medical Sciences
Outcome results
None listed