Advanced Solid Tumors
Conditions
Interventions
Treatment Group:The dose escalation study (Phase Ia) is divided into eight dose groups (A1~A8): 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, and 160 mg. The traditional "3+3" dose escalation de
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female >= 18 years and = 12 weeks; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 5. Adequate organ function and laboratory test results meeting the following criteria within 7 days prior to the first dose: (1). Hepatic Function: 1) .AST and ALT = 60 mL/min (calculated using the Cockcroft-Gault formula); (4).Hematology (without transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), or other medical supportive treatment within 14 days prior to study drug administration): 1).Hemoglobin (HGB) >= 90 g/L; 2).Platelet count (PLT) >= 100 × 10^9/L. 3).Absolute neutrophil count (ANC) >= 1.5 × 10^9/L. (5) .Cardiac Echocardiogram:Left ventricular ejection fraction (LVEF) >= 50%. 6. Negative serum pregnancy test within 3 days prior to the first dose (for women of childbearing potential). Male and female subjects of childbearing potential must agree to use effective contraception methods from the signing of the informed consent form throughout the study treatment period and for 6 months after the end of study treatment; 7. Voluntary participation in the clinical study, with understanding and provision of written informed consent, and ability to comply with clinical visits and study-related procedures.
Exclusion criteria
Exclusion criteria: 1. Allergy to LSCCB-PtNNN or any of its components; 2. Received anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, or immunotherapy within 4 weeks prior to the first administration of the investigational product, or other unmarketed investigational drug treatment, except for the following: Nitrosoureas (e.g., Carmustine, Lomustine, etc.) or Mitomycin C within 6 weeks prior; Oral fluoropyrimidines or small-molecule targeted agents within 2 weeks prior or within 5 half-lives of the drug (whichever is shorter); Chinese herbal medicines with anti-tumor indications within 2 weeks prior. Palliative radiotherapy within 7 days prior; 3. Concurrent use of drugs known to prolong the QTc interval or induce Torsades de Pointes (TdP), with the exception of antimicrobial agents used as standard therapy for the prophylaxis or treatment of infections or other such drugs deemed essential to treatment by the investigator; 4. Concurrent use of OATP1B1, OCT2, and MATE2-K substrates, other ß-lactamase inhibitors or inducers, or drugs that are substrates related to LSCCB-PtNNN (e.g., CYP2C8). 5. Major surgery within 28 days prior to the first dose; 6. Acute toxicities from prior anti-tumor therapy have not recovered to Grade 450 ms for males, >470 ms for females; (2).Any factor that may increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome in first-degree relatives, or unexplained sudden death under the age of 40, and the use of any concomitant medications known to prolong the QT interval; (3).Clinically significant arrhythmia, unstable angina, congestive heart failure (New York Heart Association [NYHA] Class III or IV), or acute myocardial infarction within 6 months prior to enrollment; (4).Any arterial thromboembolic event within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack; (5).Subjects at risk for Torsades de Pointes; any supraventricular or ventricular arrhythmia requiring treatment or intervention; (6).Uncontrolled hypertension (systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg despite regular antihypertensive medication); 8. Patients with a positive HIV test, active hepatitis B or C, or active syphilis. Subjects who are hepatitis B surface antigen (HBsAg) positive with a hepatitis B virus DNA (HBV-DNA) titer >= 1 × 10^3 IU/mL are excluded; if HBsAg positive but with HBV-DNA < 1 × 10^3 IU/mL, subjects are eligible if the investigator considers their chronic hepatitis B to be stable and not to increase the subject's risk. Subjects who are anti-hepatitis C virus (anti-HCV) antibody positive are eligible if HCV RNA is below the upper limit of normal (ULN) of the testing center; 9. Uncontrolled intercurrent illness, for example: (1).Serious infection within 4 weeks prior to study treatment, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications; or active infection requiring therapeutic oral or intra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety/Tolerability Assessment(Incidence, severity, and relationship with the investigational drug of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-related adverse events (TRAEs), and dose-limiting toxicities (DLTs).);MTD/RDEs(To determine the MTD and RDEs of LSCCB-PtNNN Injection therapy);Safety/Tolerability Assessment(changes in vital signs, ECOG score, ECG, physical examination, and laboratory tests before and after treatment); | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters (PK parameters after single-dose administration and PK parameters after multiple-dose administration);Efficacy Evaluation(Objective response rate(ORR),Duration of Response(DoR),and Disease Control Rate(DCR)following investigational drug treatment); | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed