A Single-center, Dose-escalation Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) in Study Participants With HRD-negative Epithelial Ovarian Cancer

Korábbi kezelés

• (Per interview) Judged by the investigator as unsuitable for enrollment or unable to comply with the protocol requirements, including but not limited to: persistent fever (>24 h) documented by repeated measurements or due to active, uncontrolled infection from screening to prior to drug administration.
• (Per interview) Receipt of cellular immunotherapy within the past 6 months (including: Cytokine-Induced Killer (CIK) cells, dendritic cell (DC) therapy, DC-CIK therapy, Lymphokine-Activated Killer (LAK) cells, and other cellular immunotherapies).
  • In addition to the above requirements, patients who meet any of the following criteria shall also be excluded prior to the collection of autologous peripheral blood mononuclear cells (PBMCs):
• Receipt of chemotherapy within 3 weeks prior to collection.
• Receipt of anti-angiogenic tyrosine kinase inhibitor (TKI) small-molecule drugs within 3 weeks prior to collection.
• Use of corticosteroids (or analogs) or systemic administration of immunomodulatory therapies within 3 weeks prior to collection.
• Participation in a clinical study of an investigational non-biolgical product (administered within the past 30 days or 5 half-lives, whichever is longer) or an investigational biological product (monoclonal or polyclonal antibodies) (administered within the past 4 months or 5 half-lives, whichever is longer) prior to screening.
• Study participants with insufficient sensitivity to immunotherapy as determined by tumor genetic analysis.

Más betegség

• (Per interview) A past or current diagnosis of Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).
• (Per interview) Suffering from severe or uncontrolled diseases, including but not limited to: uncontrolled ventricular arrhythmia, myocardial infarction within the recent 3 months, uncontrolled grand mal epilepsy, unstable spinal cord compression, superior vena cava syndrome, immunodeficiency (excluding splenectomy), or other diseases that the investigator deems may expose the patient to a high risk of harm.
• Positive for Human Immunodeficiency Virus (HIV) antibody, Treponema Pallidum (TP) antibody, or Hepatitis C Virus (HCV) antibody; or evidence of active hepatitis B via Hepatitis B Virus (HBV) surface antigen/HBV DNA testing.
• New York Heart Association (NYHA) Grade III-IV congestive heart failure, or clinically significant arrhythmia with poor control.
• Uncontrolled arterial hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
• (Per interview) A history of or current comorbidities including the following:a) Autoimmune disease requiring long-term (more than 2 months) systemic immunosuppressant (corticosteroid) therapy, or immune-mediated symptomatic diseases (including ulcerative colitis, Crohn's disease, rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), autoimmune vasculitis (e.g., Wegener's granulomatosis));b) A past diagnosis of immune-mediated motor neuron disease;c) A past diagnosis of Toxic Epidermal Necrolysis (TEN);d) Any psychiatric disorder (including dementia, altered mental status) that may impair the understanding and completion of informed consent and relevant questionnaires;e) Long-term use of non-inhaled corticosteroids, hydroxyurea, or immunomodulatory drugs;f) A history of other active malignant tumors within the past 5 years (excluding patients with basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast that have been completely cured and require no follow-up treatment);g) Hypothyroidism (patients with hypothyroidism requiring only thyroid hormone replacement therapy are eligible for enrollment).

Laborértékek

• (Per interview) Allergic diathesis with hypersensitivity to two or more drugs, or known hypersensitivity to any component of the personalized neoantigen-sensitized autologous dendritic cell injection (cell cryopreservation solution CS10, human albumin, 0.9% sodium chloride injection).
• Receipt of platelet or red blood cell transfusion within 3 weeks prior to collection.

Egyéb

• (Per interview) Patients with symptomatic, uncontrolled brain metastasis or leptomeningeal metastasis.
• Pregnant or lactating female study participants.
• Study participants who are judged by the investigator as unable to adhere to the trial procedures, or deemed ineligible for enrollment for any other reason.

• Female aged 18-70 years (inclusive of cut-off values); body weight ≥45 kg.
• Failed to achieve Complete Response (CR) after completion of at least first-line therapy (i.e., surgery and platinum-based chemotherapy), with abnormal CA125 levels or at least one measurable lesion confirmed by imaging assessment.
• Completed genomic and transcriptomic sequencing of tumor samples, finished the analysis of genetic mutation characteristics and immune characteristics of tumor samples, and is eligible for screening of personalized tumor neoantigens.
• Laboratory examinations must meet the following criteria: white blood cell count ≥4.0×10⁹/L; absolute lymphocyte count ≥1.0×10⁹/L; platelet count ≥80×10⁹/L; hemoglobin ≥9.0 g/L; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×Upper Limit of Normal (ULN) (≤5×ULN for patients with concurrent liver metastases); bilirubin ≤1.5×ULN (≤3×ULN for patients with Gilbert's syndrome); alkaline phosphatase (ALP) ≤2.5×ULN (≤5×ULN for patients with concurrent liver metastases); albumin ≥30 g/L; serum creatinine and/or urea <1.5 times the normal value; coagulation tests: international normalized ratio (INR) <1.7 or prolonged prothrombin time (PT) <4 seconds.
• 12-lead electrocardiogram (ECG) must meet the following criteria: no severe arrhythmia, QTcF ≤480 ms.
• Toxic and adverse reactions induced by previous treatments must have recovered to Grade ≤1 (per NCI-CTCAE v5.0), with the exception of stable Grade 2 sensory neuropathy or alopecia (per CTCAE).
• With patent vascular access and capable of undergoing peripheral blood mononuclear cell (PBMC) collection.
• Expected survival time >6 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1 (see Appendix 2).
• Fertile study participants must agree to adopt medically effective contraceptive measures throughout the trial period and for at least 6 months after the last administration; fertile study participants must have a negative pregnancy test result within 28 days prior to enrollment and at baseline.
• Study participants are able to understand the trial procedures, are willing to comply with the clinical trial protocol to complete the trial, and have signed the informed consent form (ICF).