YH02 Injection for Intra-tumor Injection Therapy in Advanced Solid Tumors With Unresponsive or Failure-Treated Cases

Summary

The preclinical pharmacological mechanism of YH02 injection is well established. By constructing a vector expressing MMP13, introducing a human S promoter, and genetically modifying the capsid protein, the virus's permeability, tumor targeting capability, and infection efficiency were significantly enhanced. Preclinical pharmacodynamic studies demonstrated that YH02 exhibits potent tumor growth inhibitory effects in various human-and murine-derived solid tumor models (including breast cancer, liver cancer, and melanoma). Given that oncolytic virus therapies already have approved products with demonstrated safety and efficacy worldwide, this study may offer potential clinical benefits for patients with advanced solid tumors who have failed standard treatments. YH02 injection has undergone an open-label, dose-escalating, and expanded Phase I clinical study in China aimed at evaluating the safety, tolerability, biodistribution characteristics, viral clearance, and immunogenicity of intratumoral administration of YH02 injection in patients with advanced solid tumors who have failed adequate standard therapy and lack effective treatment options, while preliminarily investigating its efficacy. No high-grade adverse drug reactions (ADRs) have been observed to date, nor were there any serious adverse events (SAEs), severe adverse drug reactions (SUSARs), or fatal events. The clinical safety and tolerability of this product for intratumoral administration are favorable.

Eligibility

Inclusion Criteria:

* Age: ≥18 years.
* Resectable malignant solid tumors confirmed by histology or cytology (including head and neck cancer, breast cancer, melanoma, cervical cancer, skin malignancies, salivary gland carcinoma, oropharyngeal carcinoma, etc.) should prioritize treatment options for head and neck cancer, breast cancer, and melanoma.
* After complete failure of standard treatment (disease progression or intolerance to therapy) and in the absence of effective therapeutic options.
* There must be at least one measurable lesion (according to the RECIST 1.1 criteria), and the lesion must be suitable for intratumoral injection.
* ECOG score ≤2.
* The expected survival period is ≥12 weeks.
* The subject must demonstrate adequate hematological and organ function, with all laboratory parameters evaluated within 7 days prior to the initial administration and meeting the following criteria: Hematologic system (no recent transfusion or hematopoietic stimulation therapy within 14 days): ANC ≥ 1.5 × 10⁹/L; PLT ≥ 80 × 10⁹/L; Hemoglobin (Hb) ≥ 85 g/L; Liver function: Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (≤ 3.0 × ULN for patients with Gilbert syndrome or liver metastases/hepatocellular carcinoma); Alanine aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastases or hepatocellular carcinoma: ALT ≤ 5 × ULN; Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Albumin ≥ 2.8 g/dL; Renal function: Creatinine ≤ 1.5 × ULN; or Creatinine clearance (Ccr) ≥ 30 mL/min (calculated using the Cockcroft-Gault formula, only when creatinine\> 1.5 × ULN); Coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; International normalized ratio (INR) or Prothrombin time (PT) ≤ 1.5 × ULN.
* The subject has voluntarily signed an informed consent form and demonstrates good compliance.

Exclusion Criteria:

* Patients had received antitumor therapy for the first time within 4 weeks prior to initial administration, including endocrine therapy, chemotherapy, radiotherapy, targeted therapy, immunotherapy, or traditional Chinese medicine-based antitumor treatment; or had participated in other clinical trials within 4 weeks before enrollment.

Development of any other malignant tumor other than the study tumor within 5 years prior to first use of the investigational drug, excluding locally advanced cancers that have been completely cured or are disease-free for at least 5 consecutive years, such as basal or squamous cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, or breast ductal carcinoma in situ.

* The adverse effects of previous antitumor treatments have not yet been classified as Grade ≤1 on the NCI CTCAE v5.0 grading scale (excluding toxicities such as alopecia and grade 2 neurotoxicity induced by prior platinum-based therapy, which researchers consider to pose no safety risks).
* Receiving systemic glucocorticoids (prednisone\>10 mg/day or equivalent doses of similar agents) or other immunosuppressive therapies within 2 weeks prior to initial use of the study drug, excluding the following: topical, ocular, intra-articular, intranasal, or inhaled glucocorticoid therapy; short-term (≤1 week) prophylactic use of glucocorticoids (e.g., for contrast agent allergy) or for treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reactions induced by contact allergens).
* Immuno-modulatory drugs, including but not limited to thymosin, IL-2, and interferon (IFN), were administered within 2 weeks prior to the first administration of the study drug.
* A syndrome characterized by clinically significant autoimmune diseases (excluding well-controlled hypothyroidism). Patients with vitiligo, type 1 diabetes mellitus, or psoriasis who do not require systemic treatment and have no history of recurrence in the absence of external triggers are eligible for inclusion.
* A live attenuated vaccine was administered within 4 weeks prior to the first use of the study drug.
* Has previously received oncolytic virus therapy or other gene-based therapies.
* Patients had undergone major surgical procedures or suffered severe trauma within 4 weeks prior to enrollment, or were expected to undergo significant surgery during the study period; furthermore, before the first administration of the investigational drug, all adverse events (AEs) related to surgery or major trauma had not resolved to CTCAE level ≤1 or baseline levels.
* Patients with clinical manifestations of CNS metastasis or meningeal metastasis, or other evidence indicating that the patient's CNS or meningeal metastatic lesions are not under control, shall be deemed unsuitable for enrollment by the investigator. Patients with clinical symptoms suggestive of brain or meningeal disease require computed tomography (CT) or magnetic resonance imaging (MRI) examination.
* For patients with previously treated brain metastases, inclusion may be considered if their clinical condition is stable within 4 weeks prior to enrollment, there is no evidence of new lesions or lesion progression, and they have not received glucocorticoid therapy within 1 week before the first administration.
* Has a medical history of leptomeningitis.
* Patients with a history or evidence of high-risk cardiovascular disease are eligible, including but not limited to: severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention, grade II-III atrioventricular block), a Fridericia formula-corrected QT interval (QTcF) ≥ 470 msec; acute coronary syndrome (including acute myocardial infarction and unstable angina), stroke, or other grade 3 or higher cardiovascular events occurring within 6 months prior to first administration; stent implantation within 6 months before initial use of the study drug; congestive heart failure classified as grade ≥ II according to the New York Heart Association (NYHA) criteria; echocardiographic findings of valvular morphological abnormalities (grade ≥ 2); note: patients with grade 1 valvular morphological abnormalities (e.g., mild regurgitation/stenosis) may be enrolled, but those with moderate valve thickening are excluded; left ventricular ejection fraction (LVEF) \<the institutional lower limit (or LVEF \<50% if no such limit exists); or poorly controlled blood pressure despite antihypertensive therapy (i.e., systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg).
* Virological tests: Positive for hepatitis B virus surface antigen (HBsAg); positive for hepatitis B core antibody (HBcAb) with hepatitis B virus (HBV) DNA level\> upper limit of detection (ULN); positive for hepatitis C virus antibody (HCV-Ab) with hepatitis C virus (HCV) RNA level\> ULN; positive for anti-human immunodeficiency virus antibody (Anti-HIV). Meeting any of the above criteria.
* Had an active infection requiring systemic treatment (intravenous administration) within 2 weeks prior to the first use of the investigational drug, excluding local treatments.

Patients known to have allergic reactions to any component of the YH02 injection formulation.

* Individuals with known mental disorders that may affect research compliance or substance abuse.
* Patients who have undergone or plan to undergo organ transplantation (e.g., liver transplantation).
* Patients who, according to the investigators' assessment, have other severe systemic diseases, abnormal laboratory findings, or other reasons that make them unsuitable for participation in this clinical study.

Conditions2

Interventions1

Browse More Trials