OVV-01 Intravenous and Intratumoral Injection Combined With AK112 for the Treatment of Advanced Solid Tumors

A Single-Arm, Open-Label Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of OVV-01 Administered Intravenously and Intratumorally in Combination With AK112 in Patients With Advanced Solid Tumors

This study is an open-label, multiple-route-of-administration dose-escalation clinical trial designed to evaluate the safety and preliminary efficacy of OVV-01 injection administered intravenously or intravenously plus intratumorally, either as monotherapy or in combination with AK112 injection, in subjects with advanced solid tumors.

Eligible subjects must have advanced malignant solid tumours that have been confirmed by histology or cytology and possess measurable, injectable tumour lesions, including superficial and deep lesions that can be injected under ultrasound/CT guidance.

The study comprises a screening period, a treatment period and a follow-up period. The screening period runs from the day the subject signs the ICF (Day -28) until the day before the first dose is administered (Day -1). Eligible subjects will receive intravenous (IV) therapy alone or in combination with AK112 (Part 1), or IV therapy plus intratumoral (IT) therapy alone or in combination with AK112 (Part 2). Dosing occurs on Days 1 and 3 (D1 and D3) of each two-week treatment cycle, for up to six cycles. IV and IT injections are administered on the same day. If a DLT occurs during the DLT observation period, OVV-01 administration will be discontinued. Treatment will continue until disease progression occurs, the subject develops intolerable toxicity, the subject withdraws informed consent, the subject dies or is lost to follow-up, the investigator determines that termination is in the subject's best interests, or the subject completes six consecutive cycles, whichever occurs first.

Inclusion Criteria:

1. At least 18 years of age at the time of signing the ICF; gender is not restricted.
2. Patients with advanced solid tumors confirmed by histopathological/cytological examination of the primary and/or metastatic lesions, including but not limited to: melanoma, head and neck squamous cell carcinoma, cervical cancer, osteosarcoma, nasopharyngeal carcinoma, breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, gastric cancer, etc.
3. Patients with advanced disease who have failed standard therapy, lack standard treatment options, or are medically ineligible for standard therapy. Patients must have progressed after receiving at least two standard therapies (including but not limited to targeted therapies).
4. Subjects must have at least one measurable lesion as defined by RECIST 1.1 criteria, i.e., non-lymph node lesions ≥10 mm in longest diameter and lymph node lesions ≥15 mm in shortest diameter 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 0-1, with an estimated survival of at least 12 weeks.
6. Sufficient organ and hematopoietic function.
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 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 those clinically stable for over 3 months following local treatment may be enrolled);
2. Subjects who underwent radiotherapy to the target lesion within the past 2 months (may be enrolled if the radiotherapy site progressed);
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. Largest diameter of lesions for injection >100 mm;
5. Subjects who have participated in or are currently participating in other drug or medical device clinical trials within the past 4 weeks;
6. Subjects scheduled for or who have previously undergone tissue/organ transplantation;
7. Subjects 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 screening positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with HBV-DNA above the lower limit of detection, or screening positive for HCV antibody with 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 ≥ Grade 3 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 the first dose; Received nitrosourea or mitomycin C within 6 weeks prior to the first dose; Palliative radiotherapy for non-target lesions is permitted (≥2 weeks prior to the first dose);