Advanced Solid Tumors
Conditions
Interventions
Experimental group: HX001, the dosage escalation method adopted the "3+3" dosage escalation method, with dosage groups including 0.25 mg/time, 0.5 mg/time, 1 mg/time, 2 mg/time and 4 mg/time
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent form, understand this study, and be willing and able to complete all trial procedures; 2. Aged 18 to 70 years (inclusive), any gender; 3. Patients with advanced malignant solid tumors confirmed by histology or cytology, who have failed standard treatment or have no effective treatment options; 4. According to iRECIST, have one or more measurable superficial tumor lesions and/or metastases confirmed by CT, or lesions confirmed by ultrasound that can be injected under ultrasound or CT guidance, with baseline longest diameter of injectable lesions (short diameter >=15 mm for lymph node lesions) >=10 mm, meeting the volume requirements for the first injection; 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1; 6. Expected survival time >=3 months; 7. No severe abnormalities in hematology, liver, kidney, coagulation function, or cardiac function. Screening period laboratory tests (with no administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion, or platelet transfusion support within 14 days before the test) must meet the following criteria: (1) Hematology: Absolute neutrophil count (ANC) >=1.5×10^9/L; Platelets (PLT) >=90×10^9/L; Hemoglobin (Hb) >=90 g/L; (2) Liver function: Total bilirubin (TBIL) 1.5×ULN) >=50 mL/min (calculated with Cockcroft-Gault formula); Routine urine/24-hour urine protein: urine protein qualitative =2, 24-hour urine protein <1 g; (4) Coagulation function: Prothrombin time (PT) <=1.5×ULN; Activated partial thromboplastin time (APTT) <=1.5×ULN; 8. Male and women of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 3 months after the last dose (see Appendix 11); female participants of childbearing potential must have negative blood or urine pregnancy tests within 7 days before the first dose; if HCG is elevated due to tumor, pregnancy must be ruled out by ultrasound. Women of childbearing potential are defined as females who have had menarche but have not reached menopause (except for at least 12 consecutive months of amenorrhea due to reasons other than menopause) and have not undergone sterilization surgery (removal of ovaries and/or uterus), and are considered fertile.
Exclusion criteria
Exclusion criteria: 1. No measurable lesions; 2. Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, or other anti-tumor treatments within 4 weeks or 5 half-lives (whichever is shorter) before the first administration of the investigational drug, except for the following: (1) Nitrosoureas or mitomycin C within 6 weeks before the first use of the investigational drug; (2) Oral fluoropyrimidines and small molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is shorter) before the first use of the investigational drug; (3) Traditional Chinese medicine with anti-tumor indications within 2 weeks before the first use of the investigational drug; 3. Received other investigational drugs or treatments not yet marketed within 4 weeks before the first dose; 4. Received any live vaccine within 4 weeks before the first dose; 5. Underwent major organ surgery (excluding biopsy) or experienced significant trauma within 4 weeks before the first dose; 6. Previously received cell therapy (e.g., TCR-T, CAR-T, TIL, tumor vaccine); 7. Previously received allogeneic hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation, or currently using immunosuppressants or anti-rejection medications; 8. Has any active autoimmune disease, history of autoimmune disease, or conditions/syndromes requiring systemic corticosteroid or immunosuppressive therapy (Subjects with skin diseases not requiring systemic treatment, or childhood asthma/allergies that have resolved and require no intervention in adulthood; subjects with a history of autoimmune-mediated hypothyroidism on stable thyroid hormone replacement therapy may participate); 9. Allergic to any active or inactive components of the investigational drug; 10. Adverse reactions from prior anti-tumor therapy have not resolved to CTCAE 5.0 grade 1000 IU/ml); hepatitis C virus infection (HCV-RNA > the detection limit of the research center); HIV antibody positive; positive for syphilis treponemal antibodies with positive TPPA and TRUST tests; 12. Clinical symptoms of brain metastases or meningeal metastases; 13. Presence of third-space effusion deemed uncontrollable by the investigator (e.g., large pleural effusion and/or ascites); 14. History of severe cardiovascular or cerebrovascular disease, including but not limited to: (1) severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias or second- to third-degree atrioventricular block requiring clinical intervention; (2) resting state average QTcF >470 ms on three 12-lead ECGs; (3) acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular events within 6 months prior to first dosing; (4) New York Heart Association (NYHA) functional class >= II or left ventricular ejection fraction (LVEF) =140 mmHg and/or diastolic blood pressure >=90 mmHg after treatment with two antihypertensive agents); (6) any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, difficult-to-correct hypokalem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D), or the Biological Effective Dose (BED) if the MTD is not reached;Incidence and number of Dose-Limiting Toxicities (DLTs);Incidence and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) (graded according to NCI CTCAE v5.0); | — |
Secondary
| Measure | Time frame |
|---|---|
| Measuring the levels of mRNA and expressed proteins in peripheral blood;Pharmacodynamics (PD) (percentage of major peripheral blood lymphocyte subsets (CD3, CD4, CD8, etc.));Pharmacodynamics (PD) (changes in the expression levels of activation markers of the aforementioned cell subsets, such as CD25 and CD69);Pharmacodynamics (PD): Changes in the profile of immune activation-related cytokines (e.g., IL-2, IFN-?, TNF-a, IL-6) in serum/plasma;Serum levels of total IgG antibodies against PEG, IL-12, and Fc-sOX40L;Objective Response Rate (iORR);Disease Control Rate (iDCR);Progression-Free Survival (iPFS);Duration of Relief (iDOR);Overall Survival (OS); | — |
Countries
China
Contacts
Public ContactXu Ruihua
Sun Yat-sen University Cancer Center
Outcome results
None listed