Solid Tumor
Conditions
Brief summary
BS008-001 is a multicenter, open-label phase Ib /II trial in heavily pre-treated patients with advanced solid tumors. Patients received biweekly sequential intratumoral injections of OH2 (fixed dose: 10⁷ CCID₅₀/mL) followed by BS006 (dose escalation: 10⁶-10⁷ CCID₅₀/mL), with identical volumes being injected at the same lesion. The primary endpoint is safety and tolerability; secondary endpoints included efficacy outcomes assessed by RECIST 1.1/iRECIST.
Interventions
BIOLOGICALOH2+BS006
Patients received biweekly sequential intratumoral injections of OH2 (fixed dose: 10⁷ CCID₅₀/mL) followed by BS006 (dose escalation: 10⁶-10⁷ CCID₅₀/mL), with identical volumes being injected at the same lesion.
Sponsors
Binhui Biopharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Patients with unresectable stage III or IV malignant tumors confirmed by pathology and/or cytology; such as malignant melanoma, head and neck tumors, soft tissue sarcoma, liver tumors (primary hepatocellular carcinoma or liver metastases), biliary tract tumors, pancreatic cancer, esophageal cancer, gastric cancer, etc. * 2\. Lack of standard effective treatment options, or failure of or relapse after standard treatments. * 3.Male or female patients aged 18-75 years (inclusive); Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; expected survival of more than 3 months. * 4\. At least 4 weeks have elapsed since completion of prior antitumor therapies (including endocrine therapy, chemotherapy/radiotherapy, and targeted therapy) (except radiotherapy for bone metastases); for patients treated with nitrosoureas or mitomycin, at least 6 weeks since discontinuation; and recovery from prior treatment-related adverse effects to Grade 1 or lower. * 5\. Patients who have undergone major surgery must be at least 4 weeks post-operation. * 6\. According to RECIST 1.1 criteria, at least one measurable target lesion is required, with a lesion suitable for intratumoral injection. A measurable tumor lesion is defined as having a longest diameter ≥10 mm with a scan slice thickness ≤5.0 mm; for lymph node lesions, a short-axis diameter ≥15 mm. * 7\. No severe dysfunction of major organs. * 8\. Laboratory tests: 1. White Blood Cell (WBC) ≥3.0×10⁹/L, Absolute Neutrophil Count (ANC) ≥2.0×10⁹/L, Hemoglobin (Hb) ≥90 g/L; Platelet (PLT) ≥100×10⁹/L; absolute lymphocyte count (ALC)≥0.8×10⁹/L; 2. Blood urea nitrogen (BUN) and serum creatinine ≤1.5× the upper limit of normal (ULN); 3. Total bilirubin (TBIL) ≤1.5× ULN (for patients with hepatic involvement, TBIL ≤3× ULN); 4. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5× ULN; for patients with liver metastases, ≤5× ULN; 5. Normal coagulation function (Prothrombin Time, APTT, and Thrombin Time ≤1.5× ULN). * 9\. Female subjects and their partners must use effective contraception during treatment and for 3 months after treatment. * 10\. Subjects with genital herpes must have completed herpes resolution for at least 3 months. * 11\. Voluntary signing of the informed consent form, with expected good compliance.
Exclusion criteria
* 1\. Concomitant serious medical diseases, including uncontrolled diabetes, severe infections, or active gastrointestinal ulcers. * 2\. Presence of clinically significant cardiovascular or cerebrovascular disease, including: 1. Severe or uncontrolled heart disease requiring treatment, congestive heart failure classified as New York Heart Association (NYHA) class III or IV, unstable angina not controlled by medication, a history of myocardial infarction within the past 6 months, Corrected QT Interval (QTc) on Electrocardiogram (ECG) ≥450 ms in males or ≥470 ms in females, or severe arrhythmias requiring drug treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia); 2. Placement of a cardiac stent within the past 6 months; 3. Inadequately controlled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg. * 3.Uncontrolled primary brain tumors or brain metastases. * 4\. Bone metastases (except for bone metastases that are stable and controlled after treatment), or the presence of active, clinically symptomatic brain metastases. * 5\. Active autoimmune diseases requiring systemic treatment within the past 2 years (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, etc., such as the use of disease-modifying drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for renal or pituitary insufficiency) is not considered a systemic treatment. * 6\. History of immunodeficiency (HIV antibody-positive), or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation. * 7\. Uncontrolled psychiatric disorders or infectious diseases. Lesions that do not meet the volume requirements for intratumoral injection. * 8\. Patients with active hepatitis B or hepatitis C infection: those who are HBsAg-positive or HBcAb-positive with detectable HBV DNA copies (lower limit of quantification: 500 IU/mL); HBV DNA testing is mandatory at screening for such patients. Patients with a positive anti-HCV antibody test are eligible only if HCV RNA PCR testing is negative. * 9\. Positive HIV test result. * 10\. Presence of active tuberculosis infection or other infectious diseases requiring systemic treatment. * 11\. Large amounts of pleural effusion or ascites accompanied by clinical symptoms or requiring symptomatic treatment. * 12\. Pregnant or breastfeeding women. * 13\. Use of, or ongoing treatment with, other investigational drugs or antiviral therapies within 4 weeks prior to treatment, except that patients with chronic hepatitis B receiving continuous treatment may use entecavir, tenofovir disoproxil fumarate, or adefovir dipivoxil. * 14\. Participation in another clinical study within the past 4 weeks. * 15\. Known allergy to herpes viruses or any components of the study drug. * 16\. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AE (Adverse Event) and SAE (Serious Adverse Event) | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | Toxic reactions according to the NCI-CTCAE 5.0 grading standard that occur within 3 weeks from the first administration, are judged to be drug-related by the investigator, and meet the non-hematological toxicity and hematological toxicity conditions specified in the clinical protocol |
| DLTs (Dose Limiting Toxicity) | 4 weeks from the first administration | Toxic reactions according to the NCI-CTCAE 5.0 grading standard that occur within 4 weeks from the first administration, are judged to be drug-related by the investigator, and meet the non-hematological toxicity and hematological toxicity conditions specified in the clinical protocol |
| MTD | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | If ≥2/6 subjects developed DLT, the previous dose group was MTD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR/iORR | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | Tumor response will be assessed according to RECIST 1.1 and iRECIST criteria. Descriptive statistics will be used to calculate the number and proportion of subjects achieving objective response (CR/iCR + PR/iPR) at each evaluation time point. |
| DOR/iDOR | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | The Kaplan-Meier method will be used to estimate the median duration of response (DoR). |
| PFS/iPFS | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | The Kaplan-Meier method will be used to estimate the median progression-free survival. |
| DCR/iDCR | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | umor assessments will be performed according to RECIST 1.1 and iRECIST criteria. Descriptive statistics will be used to calculate the number and proportion of subjects achieving complete response (CR/iCR), partial response (PR/iPR), and stable disease (SD/iSD) at each assessment time point. |
| OS | Through study completion, six months after the last administration of the study drug to the last enrolled subject. | The Kaplan-Meier method will be used to estimate the median overall survival (OS). |
Countries
China
Contacts
CONTACTJuan Zeng
Outcome results
None listed