Patients with advanced or recurrent HPV16 and/or 18+ cervical cancer who have failed to respond to standard treatment or are intolerant to standard treatment in the past
Conditions
Interventions
HN2201 mono therapy Group:HN2201 injection
Combination Group:HN2201 +Zimberelimab Injection
Sponsors
Hunan Provincial Maternal and Child Health Care Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The subjects have been 18 years of age or older. 2. The subjects have understood and voluntarily signed Informed Consent Form (ICF), and are able to perform follow-up the requirements and restrictions listed in ICF and this protocol. 3. The subjects have recurrent or metastatic cervical cancer diagnosed by histopathology or cytopathology, with a pathological type of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, excluding neuroendocrine carcinoma and sarcoma, and cannot be cured by surgery or local treatment. 4.The subjects must provide fresh or archived tissue samples (fresh samples are preferred), such as a paraffin block or at least 5 unstained tumor specimen slides with tumor tissue content greater than 20%. If they were unable to provide these samples, they should be enrolled when the investigator evaluated and confirmed they met other inclusion/exclusion criteria. 5. The subjects are positive for HPV-16 and/or HPV-18 infection. 6. Patients with advanced or recurrent cervical cancer failed to respond to standard treatment or were intolerant of standard treatment. 7. The expected survival time is > 12 weeks. 8. Based on CT or MRI results, the subject must have at least one measurable lesion according to RECIST 1.1 criteria. 9. The organ function levels must meet the following requirements and standards: a) Bone marrow function: white blood cell count =3×10^9/L, absolute neutrophil count =1.5×10^9/L, platelet count =90×10^9/L, hemoglobin =90 g/L; and the patient has not received the following treatments in the last week before screening: transfusions of blood or platelets, use of drugs that promote leukocyte elevation (such as colony-stimulating factors) and erythropoietin (EPO); b) Liver function: total bilirubin (TBIL=1.5×ULN), AST and ALT for patients without liver metastases are both =2.5 ULN, AST and ALT for patients with liver metastases are both =5.0×ULN, albumin =3g/dL; c) Kidney function: creatinine (Cr) =1.5 ULN, or creatinine clearance rate (Ccr) =50 mL/min (according to Cockcroft and Gault formula); urine protein =2+ (measured by reagent strip) or =1000mg/24h (urine); d) Cardiac function: left ventricular ejection fraction (LVEF) >50%; e) Coagulation function: international normalized ratio (INR) =1.5×ULN, and activated partial thromboplastin time (APTT) =1.5×ULN (if the subject is receiving anticoagulant therapy, he or she must be on a stable dose of anticoagulant and has coagulation parameters (PT/INR and APTT) within the expected range for anticoagulant treatment at the time of screening); 10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 11. Patients with reproductive potential must agree to use effective contraceptive methods from signing ICF to 120 days after the end of treatment; Female patients with reproductive potential must have a negative urine or serum pregnancy test before start of the trial
Exclusion criteria
Exclusion criteria: 1.Prior history of other malignant tumors within the past 5 years, except for cured skin basal cell carcinoma, superficial bladder cancer, and ductal carcinoma in situ of the breast. 2.The subject has received anti-tumor treatment or other experimental drug treatment within 28 days after the first administration; or has received modern Chinese medicine preparations with anti-tumor effects approved by NMPA within 2 weeks before the first administration; except for palliative radiotherapy for bone metastasis within 2 weeks before the first administration. 3.Subjects who have received cell therapy (such as TCR-T, CAR-T, TIL) in the past. 4.Subjects who need to use systemic glucocorticoid therapy (> 10 mg/day prednisone or equivalent dose of glucocorticoid) or other immunosuppressive drugs within 2 weeks before the first administration. 5.Subjects who have received drugs with immunomodulatory effects (such as thymosin, interferon, interleukin-2) within 2 weeks before the first administration. 6.Subjects who have undergone major surgery (determined by the investigator), open biopsy or significant trauma within 4 weeks before the first administration; or major surgery that needs to be performed during the study period. Systematic pelvic/para-aortic lymph node dissection for diagnosis is allowed. 7.Subjects with primary central nervous system (CNS) malignant tumors and CNS metastases; 8.Other toxicities caused by previous radiotherapy or chemotherapy drugs that persist and have not recovered to Grade =1 defined in CTCAE 5.0, except for alopecia, Grade =2 sensory neuropathy, lymphocytopenia, and endocrine diseases controlled by hormone replacement therapy. 9. History of severe cardiac disease, such as heart failure =2 at the New York Heart Association (NYHA), transmural myocardial infarction, unstable angina, poorly controlled arrhythmias, myocardial infarction within the past 6 months prior to enrollment, or arrhythmias requiring anti-arrhythmic treatment (allowable beta blockers, calcium channel blockers and digoxin). 10.Uncontrolled clinical complications including, but not limited to, uncontrolled hypertension (systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg) by two antihypertensive medications and uncontrolled type 2 diabetes mellitus by glucose-lowering therapy (fasting blood glucose =8.9 mmol/L), uncontrolled pleural or peritoneal fluid accumulation or other serious diseases requiring systemic treatment. 11.History of any active autoimmune disease, autoimmune disorder or condition requiring systemic steroid or immunosuppressive drug treatment. The following are excluded: vitiligo, alopecia areata, psoriasis or eczema without required systemic treatment; hypothyroidism due to autoimmune thyroiditis that only requires stable dose hormone replacement therapy; and type 1 diabetes mellitus that only requires stable dose insulin replacement therapy. 12.History of or ongoing thrombotic events resulting in hematological changes. 13.Active infection requiring systemic treatment (including active tuberculosis, active syphilis infection, and fungal infections requiring systemic treatment). 14.History of or evidence of significant lung disease such as uncontrolled chronic lung disease, or any interstitial lung disease, or active non-infectious pneumonia. 15.The subject is carrier of known human immunodeficiency virus (HIV); active hepatitis B infection (HBsAg positive and HBV DNA positive); active hepatitis C infection (anti-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety profile;Maximum Tolerated Dose, MTD;objective response rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| disease control rate, DCR;Duration of remission, DOR;pharmacokinetics, PK; | — |
Countries
China
Contacts
Public ContactChuqiangshu
Hunan Provincial Maternal and Child Health Care Hospital
Outcome results
None listed