A Study of SHR-1701 Plus Platinum-containing Chemotherapy With or Without BP102 (Bevacizumab) as First-line Treatment in Cervical Cancer

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy, and safety of SHR-1701 or Placebo Plus Chemotherapy With or Without BP102 (Bevacizumab) as First-Line Treatment in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer.

Official Title
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A Randomized，Double-blind，Controlled，Multi-center Phase III Clinical Study Evaluating SHR-1701 or Placebo Plus Chemotherapy With or Without BP102 (Bevacizumab) as First-Line Treatment in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: SHR-1701 + paclitaxel + cisplatin/carboplatin + BP102
* Drug: SHR-1701 + paclitaxel + cisplatin/carboplatin± BP102
* Drug: Placebo + paclitaxel + cisplatin/carboplatin ± BP102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years, female. With Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1. With a life expectancy of ≥ 12 weeks. Acute toxicities from prior anti-tumor treatments must have resolved to Grade 0-1 (per NCI CTCAE 5.0). With at least one measurable lesion as per RECIST v1.1. With histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix. Persistent, recurrent, or metastatic cervical cancer. Patients to be enrolled in Stage II are required to provide a minimum of 10 slides of fresh (preferred). Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to starting study treatment. Patients must agree and have signed the informed consent form. Exclusion Criteria: With known contraindications to paclitaxel, cisplatin, or carboplatin. With known allergies to any of the study drugs or their excipients; severe allergic reactions to other monoclonal antibodies. With inadequately treated CNS metastasis. With uncontrolled hypertension. With uncontrolled cardiac diseases or symptoms. With major vascular disease. With arterial/venous thrombotic events within 6 months prior to randomization. Have received full-dose anticoagulant or hemolytic therapy within 10 days prior to randomization. With clinically significant hemorrhage or definitive bleeding diathesis within 3 months prior to randomization. With severe, unhealed, or open wounds as well as active ulcers or untreated fractures. With any active autoimmune disease or a history of autoimmune disease that is expected to recur. Had other active malignant tumors within 5 years prior to study enrolment. With congenital or acquired immunodeficiency (such as HIV-infected patients).

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SHR-1701 or Placebo Plus Chemotherapy With or Without BP102 (Bevacizumab)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1701 + paclitaxel + cisplatin/carboplatin + BP102<br> | Drug: SHR-1701 + paclitaxel + cisplatin/carboplatin + BP102<br>* SHR-1701 + paclitaxel + cisplatin/carboplatin + BP102<br>|
| Experimental: SHR-1701 + paclitaxel + cisplatin/carboplatin ± BP102<br> | Drug: SHR-1701 + paclitaxel + cisplatin/carboplatin± BP102<br>* SHR-1701 + paclitaxel + cisplatin/carboplatin± BP102<br>|
| Placebo Comparator: Placebo + paclitaxel + cisplatin/carboplatin ± BP102<br> | Drug: Placebo + paclitaxel + cisplatin/carboplatin ± BP102<br>* Placebo + paclitaxel + cisplatin/carboplatin ± BP102<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Participants Who Experience an Adverse Event (AE) as per NCI-CTC AE 5.0（Stage I） |  | Up to approximately 21 days | 
| Incidence and severity of Participants Who Experience a Serious AE (SAE) as per NCI-CTC AE 5.0（Stage I） |  | Up to approximately 21 days | 
| Incidence and severity of Participants Who Experience an Immune-related AE (irAE) as per NCI-CTC AE 5.0（Stage I） |  | Up to approximately 21 days | 
| BIRC-assessed progression-free survival (PFS) as per RECIST v1.1（Stage II） |  | Up to approximately 10 months | 
| OS is defined as the time from randomization to death due to any cause. （Stage II） |  | Up to approximately 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator （Stage I） |  | Up to approximately 26 months | 
| Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator （Stage I） |  | Up to approximately 26 months | 
| Disease Control Rate (DCR)up to approximately 26 months（Stage I） |  | up to approximately 26 months | 
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator （Stage I） |  | Up to approximately 26 months | 
| Time to Progress(TTP) up to approximately 26 months（Stage I） | The time from the date of the first medication to the date of the first recording of tumor progression (as measured according to THE RECIST v1.1 criteria, regardless of whether treatment is continued or not). | up to approximately 26 months | 
| Overall survival (OS) up to approximately 26 months（Stage I） |  | up to approximately 26 months | 
| Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by BIRC- and investigator（Stage II） |  | Up to approximately 26 months | 
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BIRC- and investigator（Stage II） |  | Up to approximately 26 months | 
| Disease Control Rate (DCR)Per RECIST 1.1 as Assessed by BIRC- and investigator（Stage II） |  | Up to approximately 26 months | 
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by BIRC- and investigator （Stage II） |  | Up to approximately 26 months | 
| Time to Progress(TTP) up to approximately 26 months （Stage II） | The time from the date of randomization to the date of the first recording of tumor progression (as measured according to THE RECIST v1.1 criteria, regardless of whether treatment is continued or not). | up to approximately 26 months | 
| Incidence and severity of Participants Who Experience an Adverse Event (AE) as per NCI-CTC AE 5.0 （Stage II） |  | Up to approximately 26 months | 
| Incidence and severity of Participants Who Experience a Serious AE (SAE) as per NCI-CTC AE 5.0（Stage II） |  | Up to approximately 26 months | 
| Incidence and severity of Participants Who Experience an Immune-related AE (irAE) as per NCI-CTC AE 5.0（Stage II） |  | Up to approximately 26 months. |