Advanced Solid Tumors
Conditions
Interventions
Experimental group:HX011 Injection
The study adopted a combination of accelerated titration design and the classic "3+3" dose escalation design, and determined seven dose levels (including but not lim
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Voluntarily sign the informed consent form, understand this study and be willing to follow and have the ability to complete all the trial procedures. 2. Aged 18 to 70 (inclusive), gender not limited. 3. Patients with advanced malignant solid tumors confirmed by histology or cytology who have failed standard treatment, or have no effective treatment options, or have abandoned standard treatment due to unacceptable toxicity or need to terminate standard treatment. 4. According to the RECIST 1.1 standard, one or more measurable tumor lesions and/or metastases are determined by CT or MRI examination. After evaluation by the researchers, at least one lesion suitable for intratumoral injection (including superficial lesions such as skin, subcutaneous nodules, lymph nodes, etc., or deep lesions) was found, and the baseline longest diameter of the lesion to be injected was >= 10 mm (for lymph node lesions, the short diameter was >= 15 mm), meeting the volume requirements for the first injection. 5. The Eastern Cooperative Oncology Group (ECOG) score of the United States is 0 to 1. 6. Expected survival time: >=3 months. 7. There were no severe hematological abnormalities, liver, kidney, coagulation function, or cardiac function abnormalities. Laboratory tests during the screening period [no G-CSF, GM-CSF, red blood cell or platelet transfusion support therapy received within 14 days before the examination date] showed that the results met the following criteria: (1) Absolute neutrophil count (ANC) >= 1.5×10^9/L, platelet count (PLT) >= 90×10^9/L, hemoglobin (Hb) >= 90 g/L; (2) Total bilirubin (TBIL) 1.5×ULN, then creatinine clearance rate Ccr >= 50 mL/min); (5) Qualitative urine routine protein = 2+, 24-hour urine protein < 1g); (6) Prothrombin time (PT) <= 1.5×ULN, activated partial thromboplastin time (APTT) <= 1.5×ULN. 8. Men and women of childbearing age agree to take effective contraceptive measures from the date of signing the informed consent form until three months after the last medication. Women of childbearing age with a negative blood pregnancy test within 7 days before the first medication (those with elevated HCG due to tumor and confirmed by imaging as not pregnant can also be enrolled).
Exclusion criteria
Exclusion criteria: 1.1. Insufficient elution period: Relevant treatments have been received within the specified time intervals before the first administration: Anti-tumor treatments such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, and immunotherapy have been received within 4 weeks or 5 half-lives (whichever is shorter) before the first use of the study drug, except for the following items: Nitrosamuridine or mitomycin C within 6 weeks prior to the first use of the study drug; (2) Oral fluorouracil and small molecule targeted drugs should be taken within two weeks before the first use of the study drug or within five half-lives of the drug (whichever is shorter). (3) For herbal medicines/Chinese patent medicines/traditional Chinese medicines with anti-tumor indications, it is within two weeks before the first use of the study drug. 2.Received any other unapproved investigational drugs or treatments within 4 weeks prior to the first dose. 3.Received any live vaccines within 4 weeks prior to the first dose. 4.Undergone major organ surgery (excluding puncture biopsy) or experienced significant trauma within 4 weeks prior to the first dose. 5.Prior history of cell therapies (e.g., TCR-T, CAR-T, TIL, tumor vaccines). 6.Prior history of allogeneic hematopoietic stem cell/bone marrow transplantation, or solid organ transplantation, or currently using immunosuppressive drugs. 7.Concomitant active autoimmune disease, history of autoimmune disease, or conditions requiring systemic steroids or immunosuppressive therapy. 8.Known hypersensitivity to any active or inactive components of the investigational drug. 9.Toxicities from prior anti-tumor therapies have not recovered to CTCAE 6.0 Grade = 1 (except for toxicities without safety risks such as alopecia, Grade 2 peripheral neurotoxicity, or hypothyroidism stabilized on hormone replacement). 10.Active Hepatitis B (HBsAg positive and HBV-DNA > 1000 copies/mL); Hepatitis C virus infection (HCV-RNA > lower limit of detection); HIV antibody positive; Syphilis antibody positive, and both TPPA and RPR positive. 11.Symptomatic brain or meningeal metastases. 12.Uncontrolled third-space fluid accumulation (e.g., massive pleural effusion and/or ascites) as judged by the investigator. 13.Including ventricular arrhythmias requiring clinical intervention, Grade ?-? atrioventricular block ; an average QTcF > 470 ms from 3 baseline 12-lead ECGs ; acute coronary syndrome, congestive heart failure, aortic dissection, or stroke within 6 months; NYHA cardiac function class > ? ; uncontrolled hypertension (systolic BP = 160 mmHg and/or diastolic BP = 100 mmHg) ; or concomitant use of any medications known to prolong the QTc interval. 14.Active infection requiring systemic therapy within 4 weeks prior to the first dose. 15.Active tuberculosis infection detected by medical history or CT, a history of active tuberculosis within 1 year prior to enrollment, or a history of active tuberculosis infection more than 1 year ago without formal treatment. 16.Other malignancies within the past 5 years (except for cured basal cell skin cancer, non-melanoma skin cancer, or cervical carcinoma in situ). 17.Known history of alcohol or drug dependence. 18.Mental disorders or poor compliance. 19.Pregnant or lactating women. 20.Any other clinical or laboratory abnormalities that, in the opinion of the investigator, render the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Number of Dose-Limiting Toxicities (DLTs);Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D);Incidence and Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic (PD) Changes in Immune Subsets and Cytokine Profiles;Systemic Abscopal Effect (Tumor Regression in Non-injected Lesions);Progression-Free Survival (PFS), Duration of Response (DOR), and Overall Survival (OS);Immunogenicity (Anti-Drug Antibody Total IgG Levels);Pharmacokinetic (PK) Parameters in Peripheral Blood;Objective Response Rate (ORR) and Disease Control Rate (DCR); | — |
Countries
China
Contacts
Public ContactYang Kunyu
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed