Solid Tumors
Conditions
Interventions
0.1 mg/kg escalating dose groups:PA5 0.1mg/kg
0.2mg/kg escalating dose groups:PA5 0.2mg/kg
0.4,mg/kg escalating dose groups:PA5 0.4mg/kg
0.8 mg/kg escalating dose groups:PA5 0.8mg/kg
1.2 mg/kg escalating dose groups:PA5 1.2mg/kg
Dose Expansion:Carried out in 2 dose groups based on the dose-escalation results
Sponsors
Fudan University Shanghai Cancer Center
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 form prior to the initiation of any study procedures. 2.Aged = 18 years, male or female. 3.Patients with histologically or cytologically confirmed advanced/metastatic solid tumors, which are unresectable, at stage ? or ?, and for whom standard treatment has failed, is intolerable, is not available, or is judged by the investigator to be unable to confer benefit. 4.Evaluated according to RECIST version 1.1: Dose-escalation phase: At least one assessable lesion; for patients with brain metastases, there must be at least one assessable lesion outside the central nervous system (CNS). Dose-expansion phase: At least one measurable lesion; for patients with brain metastases, there must be at least one measurable lesion outside the CNS. Lesions previously treated with radiotherapy shall not be regarded as target lesions unless imaging examinations confirm clear progression of such lesions. Baseline tumor assessment scans must be performed at least 14 days after biopsy. 5.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 6.Expected survival of at least 12 weeks. 7.Brain metastases must be well-controlled (no new or untreated brain metastatic lesions; asymptomatic or stable disease for more than 4 weeks, with no requirement for steroid or anticonvulsant therapy for at least 4 weeks prior to the start of study treatment, and no obvious perilesional edema on imaging; eligibility to be determined by the investigator), and no epileptic symptoms have occurred. 8.Participants must have adequate organ and bone marrow function, meeting the following criteria: (1)Absolute neutrophil count (ANC) = 1.5 × 10?/L;Platelet count = 100 × 10?/L; Hemoglobin = 90 g/L; no blood transfusion or hematopoietic growth factor therapy administered within 7 days; (2)Total bilirubin = 1.5 × upper limit of normal (ULN); = 2 × ULN for patients with liver metastases or liver cancer; = 3.0 × ULN for patients with Gilbert's syndrome; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN; for patients with liver cancer or liver metastases: AST and ALT = 3 × ULN (dose-escalation phase only) or = 5 × ULN (dose-expansion phase only); (3)Serum creatinine = 1.5 × ULN, or creatinine clearance rate = 60 ml/min (when serum creatinine > 1.5 × ULN), calculated using the Cockcroft-Gault formula; (4)Serum albumin = 3.0 g/dL; (5)Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) = 1.5 × ULN. 9.Females of childbearing potential must have a negative serum pregnancy test within 28 days prior to the first administration of the study drug, and agree to use effective contraception from 28 days before the first dose to 3 months after the last dose of the study drug. Male participants must have undergone vasectomy, or agree to use effective contraception from 7 days before the first dose to 3 months after the last dose of the study drug and refrain from donating sperm.
Exclusion criteria
Exclusion criteria: 1.Having received chemotherapy, targeted therapy, anti-tumor Chinese herbal medicine, or palliative care within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study treatment; having undergone major surgery, radiotherapy, immunotherapy, or participated in another clinical trial within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose; having received a live-attenuated viral vaccine within 4 weeks, or an inactivated vaccine within 2 weeks prior to the first dose. 2.Presence of pleural effusion or ascites requiring clinical intervention (excluding participants with effusions that do not require drainage, or those whose effusions have been stable for 2 weeks or longer after drainage); presence of pericardial effusion (excluding small-volume pericardial effusion that has been stable for 2 weeks or longer). 3.Failure to recover from toxicities of prior anti-tumor therapies to = Grade 2 per NCI-CTCAE Version 5.0 (except for toxicities judged by the investigator to pose no safety risk, e.g., alopecia). 4.Use of drugs known to prolong the QTc interval (mainly Class Ia, Ic, and III antiarrhythmic drugs), or presence of risk factors for QTc interval prolongation. 5.Meeting any of the following criteria for cardiac function or disease: (1)Baseline electrocardiogram showing prolonged QT/QTc interval (QTcF > 450 ms for males, > 470 ms for females), calculated per the Fridericia formula. (2)Poorly controlled hypertension despite medical treatment (systolic blood pressure = 150 mmHg and/or diastolic blood pressure = 100 mmHg). (3)Congestive heart failure (CHF) of = Grade II per the New York Heart Association (NYHA) classification. (4)Clinically significant arrhythmias, including but not limited to complete left bundle branch block, second-degree atrioventricular block. (5)History of myocardial infarction within 6 months or hemorrhagic stroke within 3 months prior to screening. 6.Clinically significant active bacterial, fungal, or viral infection, including hepatitis B (hepatitis B virus surface antigen positive with HBV DNA >1000 IU/mL, or exceeding the study site's limit of detection [only if the site's limit is above 1000 IU/mL]), or hepatitis C (HCV RNA positive), active syphilis, human immunodeficiency virus infection (HIV positive); diagnosed HIV infection, and those unwilling to undergo HIV testing. 7.Other malignancies besides the indication under study, either currently or in the past, except for:Curatively treated cervical cancer of Stage IB or lower.Non-invasive basal cell or squamous cell skin cancer.Malignant melanoma with complete remission (CR) for > 10 years.Other malignant tumors with complete remission (CR) for > 5 years. 8.Pregnant or lactating women; any participant who becomes pregnant during the trial must discontinue treatment. 9.Hypersensitivity to polyethylene glycol (PEG) compounds. 10.Prior treatment with similar agents such as ADI-PEG20. 11.A history of alcohol or drug dependence, needle phobia, blood phobia, or inability to tolerate venous puncture for blood sampling. 12.Any other clinically significant disease or condition judged by the investigator to potentially affect compliance with the protocol or the participant’s ability to sign the informed consent form (ICF) (e.g., uncontrolled diabetes mellitus).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Event (AE);Serious Adverse Event;Incidence of dose-limiting toxicity (DLT) during the first cycle of drug administration; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters; | — |
Countries
China
Contacts
Public ContactHongxia Wang
Fudan University Shanghai Cancer Center
Outcome results
None listed