Adjuvant Chemoradiotherapy Followed by Zimberelimab for Locally Advanced Cervical Cancer.

Study Overview
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Brief Summary
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Locally advanced cervical cancer (stage IB3, IIA2) patients with postoperative risk factors need better treatment. We initiated a clinical study to explore the effectiveness of adjuvant chemoradiotherapy followed by Zimberelimab for these patients.

Detailed Description
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For cervical cancer, although clinical research on PD-1 monoclonal antibodies was launched relatively late, the research results so far show that PD-1 monoclonal antibodies combined with chemotherapy have a high clinical effectiveness and a relatively high efficacy in the treatment of advanced/recurrent cervical cancer. Good security. However, there is currently a lack of clinical evidence for the use of PD-1 monoclonal antibodies combined with chemoradiotherapy in the treatment of high-risk patients after cervical cancer surgery. Therefore, this study intends to explore the clinical efficacy of postoperative adjuvant radiochemotherapy followed by PD-1 monoclonal antibody in the treatment of high-risk patients with locally advanced (IB3, IIA2) cervical cancer after surgery, and provide a new solution for clinical treatment.

Official Title
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Adjuvant Chemoradiotherapy Followed by Zimberelimab for Locally Advanced Cervical Cancer (IB3, IIA2) Patients

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: Zimberelimab
* Drug: Platinum
* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma; According to FIGO2018 staging, patients with locally advanced cervical cancer (IB3, IIA2) who require concurrent radiotherapy and chemotherapy; Patients with radical surgery for cervical cancer; Female patients: 18-70 years old; ECOG physical condition score: 0 1 point; Subjects have not received previous immunotherapy; Expected survival ≥6 months; Women of reproductive age should agree to use contraceptives (such as Iuds, contraceptives, or condoms) during the study period and for 6 months after the study ends; Have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be a non-lactating patient; For adequate organ function as defined in the protocol, test samples must be collected within 7 days prior to initiation of the study therapy Subjects voluntarily joined the study, signed informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Subjects have histological subtypes other than those permitted by inclusion criteria; Severe hypersensitivity to cepalizumab and/or any of its excipients (≥ grade 3); Participate in or have participated in other clinical trials within 4 weeks before enrollment; Have received or will receive inactivated vaccine within 30 days prior to the first study treatment; Received a combination of systemic immune stimulants, colony-stimulating factors, interferon, interleukin, and vaccine within 6 weeks or 5 half-lives (if shorter) prior to initial administration; Have been diagnosed with an immune deficiency or are receiving chronic systemic steroid therapy (doses greater than 10mg daily equivalent of prednisone) or any other form of immunosuppressive therapy within 7 days prior to the first dose; Have an active autoimmune disease in the past 2 years that requires systemic treatment (such as the use of disease-modulating drugs, corticosteroids, or immunosuppressive drugs); Have a history of (non-infectious) pneumonia requiring steroid treatment or have a current (non-infectious) pneumonia; An active infection requiring systematic treatment; Known history of HIV infection; A known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as detection of HCV RNA[qualitative]) infection; Known active tuberculosis (TB; Tuberculosis) medical history; Has received allogeneic tissue/solid organ transplantation; Suffering from central nervous system metastases such as brain metastases; Patients with uncontrolled chest and abdominal fluid; Patients with mobility disorders such as pathological fractures caused by tumor bone metastasis; Insufficient hematopoietic function of bone marrow; Abnormal liver; Abnormal kidney; Bleeding risk; Cardiovascular and cerebrovascular abnormalities.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Concurrent themoradiotherapy Followed by Zimberelimab<br>Radiotherapy: Intensity modulated conformal radiation therapy (IMRT) is used for external irradiation, and the pelvic target volume dose (PTV) is: 45-50 Gy/1.8Gy/25-28f; the stump margin is positive, and after the external irradiation is completed, Additional CT-guided three-dimensional conformal brachytherapy, HR-CTV: 24--30Gy/4-5f. Concurrent chemotherapy: performed during external radiotherapy. Starting from the first week of radiochemotherapy, cisplatin 40 mg/m2 was given. Chemotherapy is given every 7 days, up to 5-6 times; Zimberelimab injection: 240 mg/time, intravenous infusion, administered every 21 days, starting within four weeks after completing concurrent chemoradiotherapy, and maintained for 8 cycles | Drug: Zimberelimab<br>* 240mg, q3w，8 cycles<br>Drug: Platinum<br>* cisplatin 40mg/m2 for 5-6 cycles<br>Radiation: radiotherapy<br>* 45-50Gy/1.8Gy/25-28f<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in tumor-related biomarkers | changes of tumor- related biomarkers (T cell receptor library profile and peripheral blood ctDNA content analysis) | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival | 5 years | 
| DFS | Disease Free Survival | 2 years | 
| AE | Adverse event | 3 years |