OVV-01 Injection Combined With AK112 Injection for the Treatment of Patients With Advanced Soft Tissue Sarcoma (STS)

A Single-Arm, Open-Label, Multicenter Clinical Study Evaluating the Safety and Efficacy of OVV-01 Injection Combined With AK112 Injection in Patients With Advanced Soft Tissue Sarcoma (STS)

The efficacy of OVV-01 injection in combination with AK112 injection in subjects with advanced soft tissue sarcoma was evaluated using ORR as the primary endpoint.

This study is an open-label, single-arm Phase II clinical trial that will enroll subjects with histologically/cytologically confirmed metastatic or recurrent unresectable soft tissue sarcoma.

Inclusion Criteria:

1. Voluntarily sign the informed consent form, understand this study, and agree to comply with the protocol and complete all trial procedures;
2. Be at least 18 years of age at the time of signing the ICF, with no gender restrictions.
3. Histologically/cytologically confirmed metastatic or recurrent unresectable soft tissue sarcoma, currently failing standard therapy (disease progression, recurrence, or intolerance to treatments such as chemotherapy, radiotherapy, or targeted therapy) or lacking standard treatment options. Participants must have progressed after receiving at least two standard therapies (including but not limited to targeted therapies). Subjects must have demonstrated failure or intolerance to anthracycline-based standard chemotherapy regimens. For specific histologic subtypes lacking standard effective chemotherapy options (e.g., alveolar soft part sarcoma), subjects may have previously received targeted therapy (e.g., anti-angiogenic agents such as anlotinib, pazopanib) with failure or intolerance.
4. Subjects must have at least one measurable lesion as defined by RECIST 1.1 criteria, i.e., non-lymph node lesions with a longest diameter ≥10 mm and lymph node lesions with a shortest diameter ≥15 mm on CT or MRI. Injectable tumor lesions must be present, including superficial lesions and deep lesions amenable to injection under ultrasound/CT/or endoscopic guidance.
5. ECOG performance status of 0-2, with an estimated survival of at least 12 weeks.
6. Sufficient organ and hematopoietic function:Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 75 × 10⁹/L (no platelet transfusion or thrombopoietin (TPO) therapy within 2 weeks prior to first dose); Hemoglobin ≥ 90 g/L (no blood transfusion within 2 weeks); Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CCr) ≥ 50 mL/min; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; for patients with liver metastases, AST and ALT < 5 × ULN; Serum total bilirubin (TBIL) ≤ 2 × ULN; International Normalized Ratio (INR) ≤ 1.5 × ULN, or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN;
7. Women of childbearing potential must have a negative pregnancy test within 7 days prior to treatment initiation.
8. Male and female subjects of childbearing potential must agree to use reliable contraception during the trial and for at least six 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 those clinically stable for over 3 months following local treatment may be enrolled);
2. Subjects who received radiotherapy to the target lesion within the past 2 months;
3. Subjects with other active malignancies within the past 5 years. Exceptions include subjects who have achieved complete remission and require no follow-up treatment, or subjects with malignancies within the scope of the indication;
4. Lesions intended for injection with a maximum diameter >100 mm;
5. Participants who have participated in or are currently participating in other drug or medical device clinical trials within the past 4 weeks;
6. Participants scheduled for or who have previously undergone tissue/organ transplantation;
7. Participants with Human Immunodeficiency Virus (HIV) infection who have experienced AIDS-related opportunistic infections within the past 12 months, or who have a CD4+ T-cell (CD4+) count < 350 cells/uL; Patients with positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) at screening, and HBV-DNA above the lower limit of detection; patients with positive HCV antibody at screening and HCV-RNA above the lower limit of detection; subjects with positive syphilis serology;
8. Subjects requiring antiviral therapy during the study period or within 5 half-lives of the first dose of antiviral therapy.
9. Subjects requiring therapeutic anticoagulant therapy during the study period.
10. Subjects with uncontrolled active infection of ≥Grade 3 severity according to CTCAE v5.0 that is clinically significant;
11. Received antineoplastic therapy (chemotherapy, radiotherapy, biologic therapy, endocrine therapy, immunotherapy, etc.) within 4 weeks prior to first dose; received small-molecule targeted therapy or oral fluorouracil-based agents within 2 weeks prior to first dose or within 5 half-lives (whichever is longer); Received Chinese herbal medicine or proprietary Chinese medicine with antitumor indications within 2 weeks prior to first dose; received nitrosourea or mitomycin C within 6 weeks prior to first dose; palliative radiotherapy for non-target lesions is permitted (≥2 weeks prior to first dose);
12. Uncontrolled hypertension, pulmonary hypertension, or unstable angina; myocardial infarction, coronary artery bypass grafting, or stent placement within 6 months prior to dosing; history of chronic heart failure at New York Heart Association (NYHA) functional class III-IV; Severe arrhythmias requiring treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia deemed by the investigator as not affecting the trial), including QTcF ≥450 ms in males or ≥470 ms in females (calculated using Fridericia's formula); cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to enrollment;
13. Active autoimmune disease or history of autoimmune disease with potential for recurrence;
14. Requirement for systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days prior to first dose or during the study period;
15. Tumors located in high-risk areas (including mucosal regions, proximity to airways, major vessels, or spinal cord) that may cause obstruction or compression due to tumor enlargement, erode major vessels due to necrosis, encase major vascular structures (e.g., carotid artery), tumors adjacent to critical neurovascular structures, or other tumors deemed unsuitable for intratumoral injection;
16. Subjects requiring administration of any live vaccine during the screening or treatment period;
17. Subjects with a history of allergy to the study drug, immunotherapy, or any component of related medications;
18. Subjects with psychiatric disorders, alcoholism, inability to abstain from smoking, drug addiction, or substance abuse;
19. Pregnant or lactating women;
20. Adverse reactions to prior antitumor therapy not yet recovered to Grade 1 (CTCAE 5.0) (excluding alopecia);
21. Severe uncontrolled medical conditions, or other circumstances deemed by the investigator to potentially interfere with study treatment, rendering the subject unsuitable for participation;
22. Other conditions deemed by the investigator to preclude eligibility.