a Polyphenol Whole Tumor Cell Vaccine in Patients With Advanced Malignant Solid Tumors

Summary

This project intends to carry out phase I clinical studies on the basis of the previous work, initially exploring the possible effective dose, evaluating its safety and tolerability, with a view to achieving long-term control of the disease, which is expected to provide more options for the treatment of patients with advanced malignant solid tumors. The development of this project will provide new ideas, strategies and theoretical basis for the research and development of whole tumor cell vaccines; at the same time, it is expected to obtain original new drugs with independent intellectual property rights.

Eligibility

Inclusion Criteria:

1. Male or female patients aged 18 to 65 years (including borderline values) at screening.
2. Advanced metastatic malignant solid tumors (skin or limb melanoma/head and neck tumors/soft tissue tumors, etc.) confirmed histologically or cytologically, with previous failure of second-line or higher treatment (refer to the China Clinical Oncology (CSCO) Melanoma Guidelines 2024, CSCO Head and Neck Tumor Guidelines 2024, and CSCO Bone and Soft Tissue Tumor Guidelines.

   Note: ① Advanced metastatic melanoma: first-line standard treatment includes dacarbazine/timozolomide ± platinum ± endo, and dabrafenib + trametinib is recommended if the BRAF V600 mutation is carried. Second-line treatment may be considered with a different drug therapy than first-line treatment, and if PD-1 monoclonal antibody is not used in the first line, pabolizumab or treprotilizumab is recommended in the second line. If tumor reduction is urgently needed, targeted drugs or chemotherapy combination regimens (paclitaxel/albumin paclitaxel ± platinum ± antivascular drugs) are preferred in the second line. If NRAS mutation is carried, tulolametinib (HL085) is recommended.

   (ii) Advanced metastatic head and neck tumors: first-line standard treatment includes pembrolizumab + cisplatin/carboplatin + 5-Fu, pembrolizumab (CPS ≥ 1), cisplatin/carboplatin + 5-Fu + cetuximab, cisplatin + docetaxel + cetuximab, and cisplatin/carboplatin + paclitaxel ± cetuximab. Second-line or salvage therapy is recommended, such as nabulizumab.

   (iii) Advanced metastatic soft tissue sarcoma: first-line standard treatment includes doxorubicin ± isocyclophosphamide chemotherapy, and second-line treatment is based on the specific type of chemotherapy or amilorotinib targeted therapy.
3. Presence of at least 1 measurable or evaluable lesion according to RECIST v1.1 criteria.
4. Eastern Cooperative Oncology Group (ECOG) physical status score: 0 to 2.
5. Expected survival ≥ 3 months.
6. Good function of major organs, and the following requirements are met by the examination indexes within 7 days prior to receiving treatment:

   ① Hemoglobin ≥80 g/L; neutrophil count \>1.5×109/L; platelet count ≥80×109/L;

   ② Total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 × ULN; if there are liver metastases, ALT or AST ≤ 5 × ULN;

   ③ Creatinine (SCr) ≤ 1.5 × ULN or creatinine clearance (CRCI) ≥ 60 mL/min (Cockcroft-Gault formula) (see 16.6 Appendix VI);

   ④ Prothrombin time (PT), International Normalized Ratio (INR) ≤ 1.5 x ULN (unless warfarin anticoagulation is being used).

   ⑤ Cardiac function: left ventricular ejection fraction (LVEF) ≥50%.
7. Able to understand and voluntarily sign a written informed consent before the trial.

Exclusion Criteria:

1. Patients with a prior history of other tumors, except for cured and non-recurrent basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ, gastrointestinal intramucosal carcinoma, and other histories of malignancies deemed by the investigator to be eligible for enrollment.
2. Patients with known concomitant cardiac clinical conditions or diseases that are not well controlled, e.g., New York Heart Association (NYHA) class II or higher heart failure (see 16.5 Appendix V), unstable angina, myocardial infarction within 6 months, supraventricular or ventricular arrhythmias that are clinically significant and require treatment or intervention.
3. Patients with previous and current objective evidence of asthma, history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severely impaired lung function.
4. Have any uncontrollable clinical disease (e.g., respiratory, circulatory, digestive, neurologic, hematologic, genitourinary, endocrine system disorders) or psychiatric disease (e.g., depression, schizophrenia) or other significant illnesses assessed by the investigator as preventing the provision of informed consent, interfering with the interpretation of the trial results, potentially posing a risk to subjects by participating in this trial, or otherwise otherwise interfere with achieving the purpose of the study.
5. Have any active autoimmune disease or a history of autoimmune disease including, but not limited to, immune-related neurological disorders, multiple sclerosis, autoimmune (demyelinating) neuropathies, Guillain-Barre Syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis-relaxation (TEN) or Stevens-Johnson syndrome (except for type I diabetes on stable doses of insulin).
6. Allergy to the test drug (including any excipients). Prior history of severe allergy to any drug, food, or vaccination, such as anaphylaxis, anaphylactic laryngeal edema, anaphylactic dyspnea, anaphylactic purpura, thrombocytopenic purpura, and localized anaphylactic necrotic reaction (Arthus reaction).
7. the existence of intradermal injection contraindications: ① injection site inflammation, trauma ulceration. ② severe bleeding, coagulation tendency, platelets or coagulation factors significantly reduced. ③ Any abnormalities or permanent body art (e.g., tattoos) at the vaccination site that, in the opinion of the investigator, would prevent observation of local reactions at the vaccination site.
8. Participation in other drug or device clinical trials within 3 months prior to screening.
9. Major surgery (minor surgery such as catheterization, protocol-required biopsy procedures, etc. is not an exclusion criterion) within 4 weeks prior to the first dose of vaccination or less than 14 days of elimination of the effects of surgery or trauma prior to enrollment, radiotherapy, targeted, immune checkpoint inhibitors, interferon, live/live attenuated vaccines, and other treatments.
10. Patients who have not recovered to NCI CTCAE ≤ grade 1 for antitumor therapy-related adverse reactions (except alopecia) after previous antitumor therapy.
11. Subjects on systemic therapy with corticosteroids (\>10 mg/day of prednisone or equivalent dose of other glucocorticoids) or other immunosuppressive agents within 14 days prior to the first dose of vaccination. Inhaled or topical steroids and adrenal hormone replacement at doses ≤ 10 mg/day prednisone efficacy dose are allowed in the absence of active autoimmune disease.
12. Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis infections, or positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), HIV antibody, and syphilitic spirochete (TP) antibody test at screening: HBsAg (+) or HBcAb (+), and HBV DNA copy number ≥ 2000 IU/mL (or the lower limit of positive test values at the host research center); HCVAb positive and HCV RNA ≥ ULN at the host research center.
13. Patient has a history of active tuberculosis (TB) (patients suspected of having active TB need to be examined on chest X-ray, sputum, and excluded by clinical signs and symptoms) or active TB; or severe acute or chronic infection requiring systemic therapy.
14. History of substance abuse or known medical, psychological, or social conditions such as alcohol or drug abuse.
15. Pregnant or breastfeeding women with a screening period up to 12 months after the full course of drug injection, a planned pregnancy in a female subject or a planned pregnancy in the partner of a male subject.
16. Any other factors that, in the opinion of the investigator, make it inappropriate for the subject to enter this trial.

Conditions4

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