relapsed/refractory advanced malignancies
Conditions
Interventions
Ia :A maximum of 48 patients will be enrolled in this phase and are planned to be divided into eight dose groups: 0.3 mg/kg, 1mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40mg/kg and 50 mg/kg. Patien
Ib:Planned to be dosed once a week continuously for 28 days until withdrawal standard. Subject sample size, tumor species and dose design will be determined by SRC based on the Phase Ia trial results.
Sponsors
Shanghai General Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 years or older; 2. Patients with locally advanced, relapsed, or refractory malignancies who have failed or are intolerant to standard treatment, as confirmed by histology or cytology, or have no effective standard treatment options.There was at least one evaluable tumor (except for stage Ia) according to response evaluation criteria in solid tumors (RECIST) v1.1; 3. Expected survival >= 12 weeks; 4. The physical status score of the Eastern Cooperative Oncology Group (ECOG) was 0-2; 5. The function of the major organs is basically normal, and the laboratory examination within 7 days or less before the first administration meets the following standards: (1) AST/ALT = 50 mL/min; (5) Hemoglobin >= 90 g/L; (6) Platelet count >= 100×10^9/L; (7) Absolute neutrophil count >= 1.5×10^9/L; 6. The blood pregnancy test of a female patient of reproductive age within 3 days prior to the first use of the test drug must be negative; Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial period and for at least 6 months after the last dose. Fertile patients are defined as sexually mature and biologically fertile; 7. Be willing to participate in clinical trials, understand and sign informed consent, and follow up and abide by research procedures on time.
Exclusion criteria
Exclusion criteria: 1. Allergy to SM3321 or its preparation components; 2. The patient received any experimental drug within 28 days prior to the first dose of SM3321; Or discontinue an investigational or anticancer drug for less than the drug's 5 half-life or 28 days, whichever is greater.Receive chemotherapy within 14 days; 3. Patients who have participated in a therapeutic clinical trial during the 28-day washout period or the 5 half-life of the drug/biologics (whichever is longer) prior to administration of the investigational drug, or who are currently participating in other investigational procedures; 4. Use of concomitant medications that may prolong QTc or induce TdP, other than antimicrobials used to prevent or treat infections as standard of care or other such medications deemed essential for treatment by the investigator; 5. Major surgery within 28 days before dosing; 6. Acute toxicity from previous antitumor therapy prior to initial administration of SM3321 did not return to the National Cancer Institute Common Terminology Criteria for Adverse Events Adverse Events (NCI CTCAE) version 5.0 450 ms for males and > 450 ms for females; (2) A variety of factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or sudden unexplained death before age 40, are using any medications with known prolonged QT interval; (3) Clinically significant arrhythmia, unstable angina, congestive heart failure (NYHA Class III or IV), or acute myocardial infarction within 6 months; (4) Any arterial thromboembolic events that occurred within the first 6 months of enrollment, including myocardial infarction death, unstable angina, cerebrovascular accident, or transient ischemic attack; (5) Uncontrolled hypertension; 8. For patients with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) whose virological status is confirmed by screening, only the following patients are infected candidates evaluated by sponsors and researchers can be included in: (1) Patients with active hepatitis B during screening: HBV DNA = 350 cells /uL; 9. Uncontrolled co-morbidities, such as: (1) Severe infections, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia, within 4 weeks prior to study initiation; Or patients who received therapeutic oral or intravenous antibiotics within two weeks prior to the start of the study and who received prophy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Tolerance;Dose-limiting toxicity;Maximum tolerated dose;Phase II recommended dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic characteristics;Immunogenicity;Antitumor activity; | — |
Countries
China
Contacts
Public ContactQi Li
Shanghai General Hospital
Outcome results
None listed