A Study of AK104/Placebo Combined With Chemoradiotherapy For The Treatment of Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of AK104 plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Combined With Chemoradiotherapy For The Treatment of Locally Advanced Cervical Cancer

Conditions
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Locally Advanced Cervical Carcinoma

Intervention / Treatment
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* Drug: AK104
* Radiation: EBRT
* Radiation: BT
* Drug: cisplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signs the written informed consent form ECOG 0-1 Life expectancy ≥ 3 months. The histological types include squamous cell carcinoma,adenocarcinoma, or adenosquamous cell carcinoma; Locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2018 Stage 3A-4A At least one measurable tumor lesion per RECIST v1.1 Adequate organ function as assessed in the laboratory tests Exclusion Criteria: Subjects with other histopathological types of cervical cancer, such as small cell carcinoma, sarcoma, etc. FIGO 2018 IVB Subjects who had previously undergone total hysterectomy Subjects who cannot receive brachytherapy Subjects with other active malignancies within 2 years prior to randomization Clinically significant hydronephrosis that cannot be relieved by nephrostomy or ureteral stenting as judged by the Investigator Any prior treatments targeting the mechanism of tumor immunity, such as immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PDL1 antibody, anti-CTLA-4 antibody, etc.), or therapy against immune costimulatory factors (e.g., antibodies directed against ICOS, CD40,CD137, GITR, OX40 targets, etc). Subjects who require systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to randomization; Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to randomization; or elective major surgical treatment required during the study Use of live vaccines within 4 weeks prior to randomization Active or potentially recurrent autoimmune disease Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation Known history of interstitial lung disease or non-infectious pneumonitis Pregnant or lactating women. Any condition that, in the opinion of the Investigator, may result in a risk when receiving the study drug.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br> | Drug: AK104<br>* q3w iv<br>Radiation: EBRT<br>* 45-50.4Gy<br>Radiation: BT<br>* ≥80Gy<br>Drug: cisplatin<br>* qw iv<br>|
| Placebo Comparator: placebo arm<br> | Radiation: EBRT<br>* 45-50.4Gy<br>Radiation: BT<br>* ≥80Gy<br>Drug: cisplatin<br>* qw iv<br>Drug: Placebo<br>* q3w iv<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival(PFS) by investigator(INV) | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 and/or biopsy | 54 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS rate at month 36 | PFS rate at month 36 | 36 months | 
| Overall Survival(OS) | OS is defined as the time from randomization to death due to any cause. | 5 years |