A Randomised, Double-blind, Placebo-controlled, Multicentre Phase Ш Clinical Study to Evaluate the Efficacy and Safety of First-line Treatment With SG001 Plus Chemotherapy±Bevacizumab Versus Placebo Plus Chemotherapy±Bevacizumab for PD-L1 Positive (CPS≥1) Women With Recurrent, or Metastatic Cervical Cancer
Overview
- Phase
- Phase 3
- Intervention
- SG001 injection
- Conditions
- Recurrent, or Metastatic Cervical Cancer With PD-L1 Positive (CPS≥1)
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 368
- Primary Endpoint
- PFS per RECIST 1.1
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This study is a randomised, double-blind, placebo-controlled, multicentre phase 3 clinical study to evaluate the efficacy and safety of SG001 plus chemotherapy±bevacizumab versus placebo plus chemotherapy±bevacizumab, as first-line treatment, in patients with PD-L1 positive (CPS≥1), Recurrent or Metastatic Cervical Cancer. The study contains a Safety Lead-in Phase in which the safety and tolerability of SG001＋Chemotherapy±Bevacizumab will be assessed prior to the Phase 3 portion of the study.
Detailed Description
The purpose of this study is to assess the efficacy and safety of SG001 plus one of four platinum-based chemotherapy regimens compared to the placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult PD-L1 positive (CPS≥1) women with recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The study include two stages: the safety run-in phase and phase Ⅲ trail. Upon completion of the first stage study, the Safety Monitoring Committee (SMC) will decide whether to proceed directly to Phase Ⅲ study. The primary study hypotheses are that the combination of SG001 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 2) Overall Survival (OS).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 and ≤ 70 on the day of signing informed consent and volunteered to participated in this study.
- •Has histologically documented recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation).
- •(Safety Lead-in)Has a measurable lesion per RECIST 1.1 via CT or MRI. (Phase 3) Has a assessable lesion per RECIST 1.1 via CT or MRI.
- •Has provided enough archival tumor tissue sample or willing to provide newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to first dose.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to first dose.
- •Has a predicted survival period ≥ 3 months assessed by investigators.
- •Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤ level 1 based on CTCAE 5.
- •Adequate organ function as defined below:
- •Blood routine tests (No blood transfusions and hematopoietic stimulators have been used, and no drugs have been used to correct blood cell counts ): Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelets ≥100 ×10\^9/L; Hemoglobin (HGB)≥9 g/dL;
- •Serum biochemical indexs: Serum creatinine ≤1.5 × ULN or \>1.5 × ULN with creatinine clearance (CCr) ≥ 60 mL/min; Serum total bilirubin (TBIL) ≤ 1.5 × ULN (Patients with Gilbert's syndrome can be up to 3 × ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 X ULN for patients with liver metastases;
Exclusion Criteria
- •Active malignancy within 2 years prior to first dose of the investigational drug, except for cervical cancer studied in this trial and any locally curable tumor that has received radical therapy (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, cervical cancer in situ, breast cancer in situ, etc).
- •History of primary immunodeficiency.
- •History of active tuberculosis.
- •Patients with any active autoimmune disease, except for patients with well-controlled type I diabetes, well-controlled hypothyroidism with hormone replacement therapy, skin diseases (such as vitiligo, psoriasis, or hair loss) without systemic treatment, or those who are not expected to relapse without external triggers.
- •Serious cardiovascular disease within 6 months prior to the first dose, including but not limited to: stable angina with functional class III-IV; unstable angina or myocardial infarction; NYHA grade III-IV congestive heart failure; severe arrhythmias requiring drug therapy (congestive heart failure allowed if ventricular rate can be controlled; severe arrhythmias requiring drug therapy (congestive heart failure is allowed if the ventricular rate can be controlled).
- •History of interstitial lung disease, or non-infectious pneumonitis requiring glucocorticoid therapy.
- •Patients with active soft meningeal disease or poorly controlled brain metastasis.
- •Prior therapy with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways including anti-PD-1, anti-PD-L1, anti-PD-L2, anti CTLA-4, OX40 agonist, and anti-CD137, etc.
- •Has received prior radiotherapy within 14 days prior to the first dose.
- •Has received prior chemosensitizer within 14 days prior to the first dose.
Arms & Interventions
safety run-in Stage(single arm) and Phase 3: SG001+Platinum-based chemotherapy±Bevacizumab
SG001 360 mg, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: SG001 injection
safety run-in Stage(single arm) and Phase 3: SG001+Platinum-based chemotherapy±Bevacizumab
SG001 360 mg, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Paclitaxel
safety run-in Stage(single arm) and Phase 3: SG001+Platinum-based chemotherapy±Bevacizumab
SG001 360 mg, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Cisplatin
safety run-in Stage(single arm) and Phase 3: SG001+Platinum-based chemotherapy±Bevacizumab
SG001 360 mg, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Carboplatin
safety run-in Stage(single arm) and Phase 3: SG001+Platinum-based chemotherapy±Bevacizumab
SG001 360 mg, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Bevacizumab injection
Phase 3: Placebo+Platinum-based chemotherapy±Bevacizumab
Placebo, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Paclitaxel
Phase 3: Placebo+Platinum-based chemotherapy±Bevacizumab
Placebo, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Cisplatin
Phase 3: Placebo+Platinum-based chemotherapy±Bevacizumab
Placebo, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Carboplatin
Phase 3: Placebo+Platinum-based chemotherapy±Bevacizumab
Placebo, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: Bevacizumab injection
Phase 3: Placebo+Platinum-based chemotherapy±Bevacizumab
Placebo, Intravenous infusion, D1, Q3W, up to approximately 2 years ; paclitaxel 175 mg/m\^2, Intravenous infusion, D1, Q3W, up to 6 cycles; cisplatin 50 mg/m\^2 or carboplatin(AUC=5) , Intravenous infusion, D1, Q3W, up to 6 cycles; with or without bevacizumab 15 mg/kg, Intravenous infusion, D1, Q3W, up to approximately 2 years All treatments will be administered until disease progression or toxicity
Intervention: SG001 placebo
Outcomes
Primary Outcomes
PFS per RECIST 1.1
Time Frame: Up to approximately 3 years
Phase 3
Safety Lead-in
Time Frame: Up to 42 days after the last patient of the lead-in phase
Incidence and grade of the TRAE、SAE and irAE
Overall survival (OS)
Time Frame: Up to approximately 3 years
Phase 3
Secondary Outcomes
- Safety Lead-in and phase 3(Up to approximately 3 years)
- TTR per RECIST 1.1(Up to approximately 3 years)
- half-time（t1/2）(Up to approximately 2 years)
- Plasma clearance（CL）(Up to approximately 2 years)
- Volume of Distribution at Steady State（Vss）(Up to approximately 2 years)
- Incidence and grade of the TRAE、SAE and irAE(Up to approximately 3 years)
- Peak Plasma Concentration（Cmax）(Up to approximately 2 years)
- DCR per RECIST 1.1(Up to approximately 3 years)
- Area under the plasma concentration versus time curve (AUC)(Up to approximately 2 years)
- PFS per iRECIST 1.1(Up to approximately 3 years)
- DOR per RECIST 1.1(Up to approximately 3 years)