Advanced epithelial-derived tumors
Conditions
Interventions
Dose-escalation study group:Intravenous administration.
The dose-escalation study was conducted using a BOIN design. The starting dose in the escalation regimen was 0.15 mg/kg Q2W. The dose increases
Dose Expansion Study Group:At least 2 dosage levels will be selected for intravenous administration based on the safety and efficacy data from the dose-escalation studies.
Sponsors
Peking University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for this clinical study: 1. The subject must fully understand the requirements of this study and voluntarily sign a written informed consent form. They must also be able to comply with the study’s medication regimen as well as all related procedures and assessments; 2. Age must be >=18 and =15 mm. The lesion must be suitable for repeated and accurate measurements. If a lesion in a previously irradiated area shows clear progression, it can also be considered a measurable target lesion; 5. The expected survival time must be >=12 weeks; 6. The Eastern Cooperative Oncology Group performance status score must be 0 or 1; 7. Subjects must have adequate function of vital organs at the time of screening. This requires that no blood transfusions, hematopoietic stimulants, or human albumin preparations have been used within 14 days prior to screening. The specific criteria are as follows: (1) Blood tests: Absolute neutrophil count >=1.5 × 10^9/L; Platelet count >=75 × 10^9/L; Hemoglobin >=90 g/L; (2) Liver function: Serum TBIL =60 mL/min, calculated using the Cockcroft-Gault formula; (5) Cardiac function: Echocardiography shows left ventricular ejection fraction greater than 50%; 8. Female subjects of childbearing age must have a negative pregnancy test within 7 days before receiving the study drug for the first time. Eligible male and female subjects must agree to use reliable contraceptive methods (hormonal, barrier methods, or abstinence) during the study and for at least 6 months after the last dose of the drug. Eligible subjects are defined as being sexually mature and biologically capable of reproducing.
Exclusion criteria
Exclusion criteria: Subjects will be excluded if they meet any of the following criteria: 1. SIG001 is administered during the washout period following previous antineoplastic therapy (4 weeks or 5 half-lives after the last dose, whichever is shorter); 2. Received radiotherapy within 28 days prior to the first dose of SIG001; 3. Acute toxicity resulting from previous antineoplastic therapy had not resolved to NCICTCAE 5.0 version grade =1 or to the baseline level specified in the inclusion criteria 4 weeks before the first dose of SIG001 (excluding hair loss or fatigue); 4. Had a history of other malignant tumors within 5 years prior to the first dose (except for non-melanoma skin basal cell carcinoma or squamous cell carcinoma that has been cured with no evidence of recurrence, breast/cervical carcinoma in situ, superficial bladder carcinoma, and other in situ cancers); 5. Subjects with any of the following cardiovascular diseases: (1) Symptomatic heart failure (New York Heart Association functional class >=2, see Appendix 4); (2) Uncontrolled hypertension despite standard treatment (systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg); (3) Resting mean corrected QT interval > 470 ms on a 12-lead electrocardiogram (QTc, using Fridericia’s correction formula) on three repeated measurements. Various clinically significant arrhythmias, conduction abnormalities, and resting ECG abnormalities, such as complete left bundle branch block, third-degree block, second-degree block, and PR interval > 250 ms. Factors that may increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome or sudden death before age 40, and use of medications known to prolong QTc; (4) Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to screening; (5) Any cause of cardiomyopathy; (6) Clinically significant valvular heart disease; (7) History of atrial or ventricular arrhythmias that require treatment; subjects with atrial fibrillation and well-controlled ventricular rate may be enrolled; (8) Transient ischemic attack or stroke within 6 months prior to screening; 6. Subjects with infectious diseases, including; (1) Acute or chronic active hepatitis B, defined as positive for hepatitis B surface antigen (HbsAg) and/or hepatitis B core antibody (HbcAb) with HBV DNA >=100 IU/mL; (2) Acute or chronic active hepatitis C, i.e., positive for HCV antibodies with HCV-RNA levels above the upper limit of the central reference range; (3) HIV-infected individuals (positive for HIV 1/2 antibodies); (4) Active syphilis or active pulmonary tuberculosis; 7. Subjects with primary central nervous system tumors, meningeal metastases, spinal cord compression, or brainstem metastases; those with untreated brain metastases or symptomatic/stable conditions can be enrolled after at least 4 weeks of stable treatment; 8. Uncontrolled comorbidities, such as: (1) Severe infections within 4 weeks prior to study initiation, including hospitalization due to infection, bacteremia, or severe pneumonia; subjects with uncontrolled active infections during screening can be enrolled if they receive prophylactic antibiotics (e.g., for urinary tract infections or chronic obstructive pulmonary disease); (2) History of interstitial lung disease, unresolved radiation pneumonitis, acute episod
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Physical examination;Vital signs;ECOG score;Electrocardiogram data;Laboratory test results: Complete blood count, blood biochemistry, coagulation function, urinalysis, thyroid function tests;Blood pregnancy test results;ECHO data;PK/PD/ADA parameters;Adverse events and concomitant medications; | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor tissue biopsy (optional) result;Tumor assessment; | — |
Countries
China
Contacts
Public ContactLin Shen
Peking University Cancer Hospital
Outcome results
None listed