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

Study Overview
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Brief Summary
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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.

Detailed Description
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This study will include 19 patients with locally advanced cervical cancer to explore the efficacy and safety of Zimberelimab in combination with concurrent radiotherapy for them.

Official Title
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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

Conditions
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Locally Advanced Cervical Cancer

Intervention / Treatment
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* Drug: zimberelimab combined With concurrent radiotherapy and chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FIGO 2018 stage IIB to IVA cervical cancer; Cervical squamous cell carcinoma, cervical adenocarcinoma or cervical adenosquamous carcinoma confirmed by histology; Have not received any radiotherapy for cervical cancer in the past, and have not received immunotherapy; Have measurable lesions (according to RECIST v1.1 standard); ECOG score: 0   1; 18 75 years old (calculated on the day of signing the informed consent); The estimated survival period exceeds 6 months; 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; Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within ● 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; 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: The subjects have other histological subtypes except those permitted by inclusion criteria 2; Bilateral hydronephrosis, unless at least one side has been implanted with a stent or solved by a positioned nephrostomy; Those who are allergic to gadolinium, a common non-ionic CT contrast agent and a magnetic resonance contrast agent Have anatomical structure or tumor geometry or any other reasons or contraindications that cannot be treated with intracavitary brachytherapy or intracavitary and implantable brachytherapy; Severe hypersensitivity (≥ grade 3) to cepalimumab and / or any of its excipients; Participated in or had participated in clinical trials within 4 weeks before randomization; Have been vaccinated or will be vaccinated with live vaccine within 30 days before the first study treatment; 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; 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; Active autoimmune diseases requiring systemic treatment during the past two years (such as the use of disease regulating drugs, corticosteroids or immunosuppressive drugs); Have a history of (non infectious) pneumonia requiring steroid treatment or currently have (non infectious) pneumonia; Active infection requiring systematic treatment; Known HIV infection history; Known hepatitis B (defined as HBsAg reactivity) or known active hepatitis C virus (defined as detection of HCV RNA [qualitative]) infection history; Known history of active tuberculosis (TB; Mycobacterium tuberculosis); Received allogeneic tissue / solid organ transplantation; Central nervous system metastasis such as tumor brain metastasis; Patients with uncontrolled hydrothorax and ascites; Patients with movement disorders such as pathological fractures caused by tumor bone metastasis; Insufficient hematopoietic function of bone marrow (without blood transfusion within 14 days): Abnormal liver: Abnormal kidney: Risk of bleeding: Cardiovascular and cerebrovascular abnormalities:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zimberelimab plus concurrent radiotherapy and chemotherapy<br>19 patients will treated with zimberelimab plus concurrent radiotherapy and chemotherapy | Drug: zimberelimab combined With concurrent radiotherapy and chemotherapy<br>* zimberelimab: 240 mg Q2W Intravenous drip，The maximum duration of medication shall not exceed one years; chemotherapy: Starting from the first week of radiotherapy and chemotherapy, cisplatin 40mg/m2 and paclitaxel 35mg/m2 were given intravenously for 30-60min; Radiotherapy: intensity modulated radiation therapy (IMRT) was used for external irradiation. The total dose of pelvic cavity and lymph drainage planning target area (PTV) was 45-50 gy/25-28f. The metastatic lymph nodes should be able to supplement or synchronously push 10-15 Gy; The internal irradiation was started within 2 weeks after the end of external irradiation treatment. The image-guided three-dimensional brachytherapy was used, and 30-40gy was added to make the total dose of point a reach 80-85 Gy, twice a week, 5-6gy each time. All radiotherapy was completed within 8 weeks.<br>* Other names: GSL-010;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate based on RECIST v1.1 | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | adverse events evaluation based on NCI-CTCAE 5.0 | two years | 
| DCR | Disease control rate evaluation based on RECIST v1.1 | one year | 
| OS | overall survival time | three years | 
| PFS | Progression free survival time | two years |