A Study of GLS-010 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled phase III study to evaluate GLS-010 plus platinum-containing chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer.

Detailed Description
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This is a randomized, double-blind, placebo-controlled phase III study，aimed to evaluate the efficacy and safety of GLS-010 plus platinum-containing chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer.All enrolled patients will be randomly divided into 2 groups and continuously treated until any event that meets the criteria for end of the clinical trial.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate GLS-010 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer

Conditions
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Persistent, Recurrent, or Metastatic Cervical Cancer

Intervention / Treatment
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* Drug: GLS-010
* Drug: Placebo
* Drug: paclitaxel
* Drug: cisplatin
* Drug: carboplatin
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent form. Women aged ≥ 18 and ≤ 75 years. ECOG of 0 or 1. Life expectancy ≥ 12 weeks. Cervical cancer patients with histologically confirmed PD-L1 positive (CPS ≥ 1),.The histological types include squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. No prior systemic therapy for persistent, recurrent or metastatic ([FIGO] Stage IVB) disease,not amenable to curative surgery or concurrent chemoradiotherapy. At least one measurable tumor lesion per RECIST v1.1; lesions previously treated with radiotherapy or other loco-regional therapy are not considered as target lesions unless the lesion has unequivocal progression or the biopsy is obtained to confirm maligancy. Subjects must have adequate organ function. Female subjects of childbearing potential must have a negative serum pregnancy test prior to the first dose. Female subject of childbearing potential must use acceptable effective methods of contraception from screening and must agree to continue these precautions until 6 months after the last dose of study drug. Exclusion Criteria: Patients with the opportunity to be cured by surgery and radiotherapy. Received with concurrent chemoradiotherapy, adjuvant chemotherapy,neo- adjuvant chemotherapy within 4 weeks prior to randomization. Active central nervous system (CNS) metastasis. Patients with other malignancies prior to randomization. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast cancer) that have been cured are not excluded. Has an active autoimmune disease that has required systemic treatment. With active serious infections. Subjects with HIV infection ,active hepatitis B virus infection, active hepatitis C virus infection,active tuberculosis infection,active syphilis . Has not recovered adequately from toxicity and/or complications from surgery prior to randomization. . . Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab. Have received any investigational treatment in other clinical trials within 4 weeks prior to randomization. Pregnant or lactating women,or women may become pregnant during treatment. Has had an allogeneic tissue/solid organ/ hematopoietic stem cells transplant. History of nervous system and mental disease. History of drug abuse. The patient is not suitable to participate the study in the opinion of the investigator.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLS-010+chemotherapy± bevacizumab<br>GLS-010 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab | Drug: GLS-010<br>* IV infusion<br>Drug: Placebo<br>* IV infusion<br>Drug: paclitaxel<br>* IV infusion<br>Drug: cisplatin<br>* IV infusion<br>Drug: carboplatin<br>* IV infusion<br>|
| Placebo Comparator: Placebo+chemotherapy± bevacizumab<br>Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab | Drug: Placebo<br>* IV infusion<br>Drug: paclitaxel<br>* IV infusion<br>Drug: cisplatin<br>* IV infusion<br>Drug: carboplatin<br>* IV infusion<br>Drug: bevacizumab<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | 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. | Up to 2 years | 
| Objective Response Rate (ORR) | Proportion of subjects who have a complete or partial response relative to baseline based on RECIST 1.1 criteria. | Up to 2 years | 
| Duration of Response (DOR) | Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria. | Up to 2 years | 
| Disease Control Rate (DCR) | DCR defined as the proportion of subjects' response of CR, PR, or SD based on RECIST v1.1 criteria. | Up to 2 years | 
| Time to Response（TTR） | TTR defined as the time from the date of randomization to the date when the response criteria are first met, based on RECIST v1.1 criteria. | Up to 2 years | 
| Number of subjects with adverse events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment | From the time of signed informed consent to 90 days after end of treatment. | 
| Quality of life (QoL) | EORTC QLQ-C30 will be used. | Up to 2 years |