Zimberelimab Combined With Concurrent Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer

• Status: Recruiting
• Trial end date: 2025-07-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is a prospective, single arm, phase II clinical study on the treatment of locally advanced cervical cancer (Ⅱ B to Ⅳ a) with Zimberelimab combined with concurrent radiotherapy and chemotherapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Zhongshan Hospital

Criteria

Inclusion Criteria:

1. FIGO 2018 stage IIB to IVA cervical cancer;

2. cervical squamous cell carcinoma, cervical adenocarcinoma or cervical adenosquamous carcinoma confirmed by histology;

3. have not received any radiotherapy for cervical cancer in the past, and have not received immunotherapy;

4. have measurable lesions (according to RECIST v1.1 standard);

5. ECoG score: 0 ~ 1; 6.18~75 years old (calculated on the day of signing the informed consent);

7. the estimated survival period exceeds 6 months; 8. before enrollment, try to provide enough tumor tissue samples (archived or fresh biopsy samples) to evaluate and confirm the expression of PD-L1 and to detect other biomarkers; Considering the accessibility of clinical specimens, there is no mandatory requirement for specimens; 9. women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; Within 7 days before the study was enrolled, the serum or urine pregnancy test was negative, and must be non lactating patients; 10. for the full organ function defined in the protocol, the test samples must be collected within 7 days before the start of the study treatment; The patients volunteered to join the study and signed the informed consent form.

Exclusion Criteria:

• 1. the subjects have other histological subtypes except those permitted by inclusion criteria 2; 2. bilateral hydronephrosis, unless at least one side has been implanted with a stent or solved by a positioned nephrostomy; 3. those who are allergic to gadolinium, a common non-ionic CT contrast agent and a magnetic resonance contrast agent 4. have anatomical structure or tumor geometry or any other reasons or contraindications that cannot be treated with intracavitary brachytherapy or intracavitary and implantable brachytherapy; 5. severe hypersensitivity (≥ grade 3) to cepalimumab and / or any of its excipients; 6. participated in or had participated in clinical trials within 4 weeks before randomization; 7. have been vaccinated or will be vaccinated with live vaccine within 30 days before the first study treatment; 8. have received systemic immune stimulant, colony stimulating factor, interferon, interleukin and vaccine combination treatment within 6 weeks or 5 half lives (whichever is shorter) before the first administration; 9. within 7 days before the first administration, the patient has been diagnosed with immune deficiency or is receiving chronic systemic steroid therapy (the dose exceeds 10mg prednisone equivalent per day) or any other form of immunosuppressive therapy; 10. active autoimmune diseases requiring systemic treatment during the past two years (such as the use of disease regulating drugs, corticosteroids or immunosuppressive drugs); 11. have a history of (non infectious) pneumonia requiring steroid treatment or currently have (non infectious) pneumonia; 12. active infection requiring systematic treatment;

13. known HIV infection history; 14. known hepatitis B (defined as HBsAg reactivity) or known active hepatitis C virus (defined as detection of HCV RNA [qualitative]) infection history; 15. known history of active tuberculosis (TB; Mycobacterium tuberculosis); 16. received allogeneic tissue / solid organ transplantation; 17. central nervous system metastasis such as tumor brain metastasis; 18. patients with uncontrolled hydrothorax and ascites; 19. patients with movement disorders such as pathological fractures caused by tumor bone metastasis; 20. insufficient hematopoietic function of bone marrow (without blood transfusion within 14 days):

1. Absolute neutrophil count (ANC) <1.5 × 109 /L；

2. Platelet <100 × 109 /L；

3. Hemoglobin <9 g/dl. 21. abnormal liver:

1. Alt, AST or alp>2.5 in the absence of liver metastasis × Upper limit of normal value reference range (ULN); Alt, AST or alp>5 in liver metastasis × ULN；

2. Serum total bilirubin >1.5 × ULN (patients with Gilber syndrome >3 × ULN）；

3. Decompensated cirrhosis (child Pugh liver function rating is B or C);

4. Hepatitis B surface antigen (HBsAg) positive and HBV DNA copy number ≥ 2000 iu/ml (HBsAg positive and HBV DNA copy number <2000 iu/ml require at least 2 weeks of anti HBV treatment before the first administration);

5. Hepatitis C virus (HCV) antibody was positive and HCV RNA was positive. 22. abnormal kidney:

1. Serum creatinine >1.5 × Creatinine clearance estimated by ULN or Cockcroft Gault glomerular filtration formula was <60 ml/ min;

2. Urine routine examination showed that urine protein was ≥++, and the 24-hour urine protein was confirmed to be >1.0 G;

3. Renal failure requires hemodialysis or peritoneal dialysis;

4. Previous history of nephrotic syndrome. 23. risk of bleeding:

1. Abnormal coagulation function: partially activated prothrombin time (APTT) or thrombin time (TT) >1.5 × ULN, or international normalized ratio (INR) >1.5 (subjects requiring anticoagulation therapy >2.5);

2. Have bleeding (hemoptysis), coagulation diseases or are using warfarin, aspirin, low molecular weight heparin and other antiplatelet agglutination drugs (except for preventive drugs with aspirin ≤ 100 mg/d);

3. Patients with any physical signs or history of bleeding, regardless of severity;

4. Active gastrointestinal bleeding, manifested as hematemesis, bloody stool or Black stool, no evidence of regression according to endoscopy or colonoscopy;

5. Any CTCAE ≥ grade 3 bleeding or bleeding event occurred within 4 weeks before the first administration.

24. cardiovascular and cerebrovascular abnormalities:

1. Subjects with any of the following conditions within 12 months before the first administration: ≥ grade II myocardial ischemia or myocardial infarction, arrhythmia, ≥ grade III cardiac insufficiency, uncontrolled angina pectoris, coronary artery / peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack;

2. Deep vein thrombosis or pulmonary embolism within 6 months before the first administration;

3. Left ventricular ejection fraction (LVEF) <50% assessed by Doppler ultrasound;

4. Fridericia corrected QTc interval (QTCF) mean (obtain at least continuous 3 ECG tests): female ≥ 470 MS;

5. There was hypertension that could not be controlled by drugs (systolic blood pressure ≥ 150 mmHg and diastolic blood pressure ≥ 100 mmHg were measured at least twice).

According to the judgment of the researcher, there are other factors that may affect the results of the study or cause the forced termination of the study, such as alcoholism, drug abuse, other serious diseases (including mental diseases) requiring combined treatment, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects