A Study of the Safety and Efficacy of the Intravenous and Intratumoral Injection of OVV-01 in Patients With Advanced Solid Tumours.

A Single-Arm, Open-Label, Dose Escalation Phase I Study of OVV-01 Intravenous and Intratumoral Injection to Evaluate the Safety, Tolerability, and Preliminary Efficacy in Patients With Advanced Solid Tumors

This is an open-label, single-arm, dose escalation clinical study to evaluate the safety and preliminary efficacy of OVV-01 Injection in patients with advanced solid tumors, following both intravenous (iv.) and intratumoral (it.) injections. This study consists of two parts: Part 1 is a dose escalation study of iv. administration; Part 2 is a dose escalation study of iv. and it. administration.

Inclusion Criteria:

1. Be willing to sign the ICF, be able to understand the study, and be willing to follow the protocol and complete all the study procedures;

2. Males or females aged ≥18 years when signing the ICF;

3. Patients with advanced solid tumors (including but not limited to melanoma, squamous cell carcinoma of head and neck, cervix carcinoma, bone sarcoma, nasopharyngeal cancer, breast cancer, lung cancer, colorectal cancer, hepatic cancer, and gastric cancer) as histopathologically or cytologically confirmed by primary lesions and/or metastases; Patients with unresectable locally advanced disease will be included, while patients with resectable disease will be excluded.

4. Patients who experienced treatment failure to standard of care, have no available standard of care, or are not suitable for standard of care due to medical reasons. Patients need to have progressed on at least two lines of standard of care therapy including but not limited to targeted therapy. For example, patients with metastatic or unresectable advanced melanoma who experienced treatment failure to standard of care such as anti-PD-1 antibody (patients harboring BRAF mutations who experienced treatment failure to BRAF and MEK inhibitors); patients with recurrent or metastatic advanced squamous cell carcinoma of head and neck who may have experienced standard treatment failure approved to anti-PD-1 monoclonal antibody and platinum-based chemotherapy; patients with recurrent or metastatic osteosarcoma who experienced treatment failure to chemotherapy drugs (including high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, etc.); patients with colorectal cancer who have received standard of care fluoropyrimidine, oxaliplatin, Bevacizumab, and irinotecan-based chemotherapy, patients with wild-type KRAS who have received anti-EGFR, and patients with microsatellite instability-high disease who have received at least one prior immune checkpoint inhibitor; patients with breast cancer (including HR positive, HER2 +, and triple negative breast cancer) who have received at least 2 prior lines which should include taxane and/or anthracycline-based therapy where appropriate and an approved checkpoint inhibitor;

5. Patients with at least one measurable lesion per RECIST v1.1, i.e., the length of non-lymph node lesion ≥10 mm or the short diameter of lymph node lesion ≥15 mm according to computed tomography (CT) or magnetic resonance imaging (MRI); The patient should also have injected tumor lesions for Part 2, including cutaneous or subcutaneous visible nodal lesions or lesions palpable deemed injectable, and hepatic lesions or non-subcutaneous lymph nodes such as retroperitoneal. These lesions should be deemed feasible for injection either directly (palpable subcutaneous tumors) by a qualified investigator or under CT or ultrasound guidance (based on size, location, and visibility); All injected tumors should be > 1 cm in size;

6. Patients with an ECOG score of 0-1 and an expected survival of at least 12 weeks;

7. Patients with adequate organ and hematopoietic function:

   ANC ≥1.5×10 9/L; Platelet count ≥75×10 9/L (no platelet transfusion or thrombopoietin [TPO] within 2 weeks prior to the first dose); Haemoglobin ≥90 g/L (no blood transfusion within 2 weeks); Serum creatinine ≤1.5×ULN or endogenous creatinine clearance (CCr) ≥50 mL/min; AST and ALT ≤3.0×ULN; AST and ALT ≤5×ULN for patients with liver metastases; Serum TBIL ≤2×ULN; International normalized ratio (INR) ≤1.5×ULN or activated partial thromboplastin time (APTT) ≤1.5×ULN;

8. Female patients of childbearing potential must have a negative pregnancy test result within 7 days prior to the study treatment;

9. Male patients of reproductive potential and female patients of childbearing potential must agree to use a reliable contraceptive method during the study and at least 6 months after the last dose.

Exclusion Criteria:

1. Patients with known brain metastases and/or clinically suspected brain metastases (however, patients with asymptomatic brain metastases or who have been clinically stable for more than 3 months after local treatment can be enrolled);

2. Patients who received radiotherapy for the target lesion in the past 2 months;

3. Patients with other active malignancies in the past 5 years shall be excluded, with the exceptions for those who are completely cured and do not require follow-up treatment, and those with study indications;

4. The longest diameter of the injected lesion is >100 mm for Part 2;

5. Patients participated (in the past 4 weeks) or are participating in clinical studies of the other drugs or medical devices;

6. Patients who plan to receive or received tissue or organ transplant;

7. Patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency (AID)-related opportunistic infection within 12 months, or CD4+ T-cell (CD4+) count <350 cells/uL; patients with positive results for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), and a hepatitis B virus deoxyribonucleic acid (HBV-DNA) level higher than the lower limit of detection at screening; patients with positive result for hepatitis C virus (HCV) antibody and a hepatitis C virus ribonucleic acid (HCV-RNA) level higher than the lower limit of detection at screening; patients with positive serology result for treponema pallidum;

8. Patients requiring antivirals during the study or those who are within 5 half-lives of antivirals at the time of the first dose of the study drug;

9. Patients requiring therapeutic anticoagulation during the study;

10. Patients with uncontrolled Grade ≥3 active infection and significant clinical relevance per CTCAE v5.0;

11. Patients who received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor drugs within 4 weeks prior to the first dose; small molecule targeted therapy and oral dose of fluorouracils within 2 weeks or 5 half-lives (whichever longer) prior to the first dose; Chinese herbal medicines or Chinese patent medicines with anti-tumor indications within 2 weeks prior to the first dose; nitrosourea or mitomycin C within 6 weeks prior to the first dose; however, patients who received palliative radiotherapy for non-target lesions are allowed (≥2 weeks prior to the first dose);

12. Uncontrolled hypertension, pulmonary arterial hypertension or angina unstable; myocardial infarction, bypass or stent surgery within 6 months prior to the first dose; history of Grade 3-4 chronic heart failure according to New York Heart Association (NYHA) criteria; serious arrhythmia requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia that have no effect on the study as assessed by the investigator), including QTcF ≥450 ms for males and ≥470 ms for females (calculated by Fridericia's formula); cerebrovascular accident (CVA) or transient ischaemic attack (TIA) within 6 months prior to enrollment;

13. Patients with active autoimmune disease or history of autoimmune disease that may relapse, however, patients with the following diseases are not excluded and may be further screened:

    Type 1 diabetes mellitus; Thyroid function decreased (if controlled with hormone replacement therapy only); Controlled coeliac disease; Skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia); Any other disease that does not recur without an external triggering factor;

14. Patients who require systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose or during the study, with the following exceptions:

    Adrenaline replacement steroids (prednisone ≤10 mg/day or equivalent); Topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids; Prophylactic short-term (≤7 days) use of corticosteroids (e.g., allergy to contrast media) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reactions caused by contact allergens);

15. Patients have tumors positioned in high-risk locations, including mucosal regions or proximity airways, major blood vessels, or spinal cord that may cause occlusion or compression upon tumor swelling or erosion into major vessels due to necrosis or encapsulated major vascular structures like the carotid artery, or adjacent to important neurovascular structures, or other tumors considered unsuitable for intratumoral injection (Part 2);

16. Patients requiring any live vaccines during the screening and treatment periods;

17. Patients who are allergic to any components of the study drug, immunotherapy or related drugs;

18. Patients who have mental illness, alcoholism, failure to quit smoking, drug use or drug abuse;

19. Pregnant or breast-feeding women;

20. Patients with toxicities (except for alopecia) caused by prior anti-tumor therapies not yet recovered to CTCAE v5.0 Grade 1;

21. Patients with serious, uncontrolled diseases or other conditions that may affect the study treatment and are not suitable for this study as assessed by the investigator;

22. Patients with other conditions that are not suitable for enrollment in the opinion of the investigator.