Safety and Efficacy of Recombinant Oncolytic Adenovirus L-IFN Injection in Relapsed/Refractory Solid Tumors Clinical Study

Safety and Efficacy of Recombinant L-IFN Adenovirus Injection in Relapsed/Refractory Solid Tumors: a Single/Multicenter, Dose-increasing, Cohort Extension Clinical Study

This is an open-label, dose escalation study of the safety and tolerability of Recombinant oncolytic adenovirus L-IFN injection（YSCH-01） when administered via intratumoral injection in patients with advanced solid tumors. The purpose of this study is to assess the safety and tolerability of Recombinant L-IFN adenovirus injectionand to determine the recommended phase 1 dose for further study. The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of Recombinant L-IFN adenovirus injection

This is an investigator initiated , open-label, study of Recombinant oncolytic adenovirus L-IFN injection given via intratumoral (IT) injection as a single agent in participants with advanced solid tumors. The study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of Recombinant L-IFN adenovirus injection. Total enrollment will depend on the toxicities and/or activity observed, with approximately19-28 evaluable participants enrolled.

The primary study objective is to determine the safety, tolerability, and maximum tolerated dose (MTD) of intratumoral administration of Recombinant oncolytic adenovirus L-IFN injection as a single agent. Secondary objectives will assess efficacy overall response rate, as well as disease control rate, progression free survival, duration of response, and anti-tumor immune responses.

Inclusion Criteria:

1. Male or female aged ≥ 18 and ≤ 75 years;
2. Patients with advanced malignant solid tumors, histologically or cytologically confirmed, who have failed standard therapy, have no standard therapy, are not eligible for standard therapy at this stage, or have refused standard therapy；
3. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the length of non-lymph node lesion ≥10 mm or the short diameter of lymph node lesion ≥15 mm according to CT or MRI cross-sectional images;CT scan of the longest axis of measurable lesions ≥10 mm (CT scan thickness ≤5 mm)；
4. There were injectable tumor lesions that met the requirements of the current dose group, including superficial lesions and deep lesions that could be injected under the guidance of B-ultrasound /CT；
5. ECOG score of 0 ~ 2;
6. Sufficient hematopoietic capacity: ANC ≥1.0 ×10^9/L (no short-acting albino within 1 week, no long-acting albino within 2 weeks), platelet count ≥75 ×10^9/L, HGB > 80 g/L (no blood transfusion within 2 weeks)；
7. Adequate liver and kidney function: AST and ALT ≤3 times ULN in patients without liver metastasis, ≤5 times ULN in patients with liver metastasis; Total bilirubin ≤1.5 ULN (excluding hyperbilirubinemia or hyperbilirubin of non-liver origin);Creatinine ≤2.0 ULN and creatinine clearance and creatinine clearance ≥40 mL/min;
8. Eligible and fertile patients (male and female) must agree to use a reliable contraceptive method during the trial and for at least 90 days after the last dose; Women of childbearing age (15-49 years) must have a negative pregnancy test within 7 days before starting treatment;
9. PT or INR <1.5 ULN, and APTT <1.5 ULN；
10. Expect to live at least 12 weeks；

Exclusion Criteria:

1. Received any antineoplastic therapy within 2 weeks prior to initial treatment；

2. Systemic diseases that have not been stably controlled after treatment, such as diabetes, serious organic cardiovascular and cerebrovascular diseases, cardiac insufficiency, hypertension, heart block above ⅱ degree, myocardial infarction within 6 months, cerebral infarction within 6 months, etc.

3. Pregnancy or lactation;

4. Uncontrolled infectious diseases, such as baseline HBV DNA≥2000 IU/ml, anti-HIV positive, HCV-RNA positive;

5. Other active infections of significant clinical significance;

6. Subjects with other active malignancies within the past 5 years, such as basal or squamous skin cancer, superficial bladder cancer, or breast cancer in situ, that have been completely cured and do not require follow-up treatment are excluded;

7. Severe autoimmune diseases such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, or Wegener's granuloma require long-term (more than 2 months) systemic immunosuppressive therapy, but subjects with the following conditions are admitted:

   Autoimmune hypothyroidism requiring only hormone replacement therapy; Skin disorders that do not require systemic treatment (e.g., eczema, a rash of less than 10% of the body surface);

8. Subjects with allergic constitution, allergy to immunotherapy or related drugs;

9. Organ failure; Coronary heart: grades ⅲ and ⅳ;Or hypertension that cannot be controlled by standard treatment, a history of myocarditis or myocardial infarction within one year; Gallo liver: achieves grade C on the Child-Turcotte-Pugh liver function scale; Gallonic kidney: renal failure and uremia; Lung: symptoms of severe respiratory failure; Brain unconsciously: people with consciousness disorder have active brain metastases;

10. Patients with active bleeding and thrombotic diseases requiring treatment;

11. Patients with uncontrollable pleural and abdominal effusion requiring clinical treatment or intervention;

12. Subjects requiring systemic corticosteroids (equivalent to >10 mg prednisone/day) within 14 days prior to enrollment or during the study period;

    The following conditions are allowed to join the group:

    Allow subjects to use topical or inhaled corticosteroids; Allows short-term (≤7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune allergic diseases;

13. Subject suffering from any mental illness, including dementia, altered mental state, that may affect informed consent and understanding of the relevant questionnaire;

14. Participated in clinical trials of other drugs or medical devices within 4 weeks;

15. If the investigator determines that they have a serious and uncontrollable disease or other conditions that may affect their acceptance of this study, they are not considered suitable for this study.