A Phase III, Randomized, Placebo Controlled, Multicenter, Double-Blind Study Comparing Toripalimab Injection (JS001) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 289
- 试验地点
- 32
- 主要终点
- IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1
研究概览
简要总结
This is a randomized, placebo-controlled, multi-center, double blinded, Phase III study to determine the efficacy and safety of TORIPALIMAB INJECTIO（JS001） in combination with gemcitabine/cisplatin compared with placebo in combination with gemcitabine/cisplatin as first-line treatment in patients with histological/cytological confirmation of recurrent or metastatic NPC. The primary endpoint is PFS in all patients. Approximately 280 patients who fulfill all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to one of the two treatment arms. patients will be randomly assigned to the combination of JS001 (Arm A) or placebo (Arm B) with gemcitabine and cisplatin given every 3 weeks (Q3W) in 3-week cycles.
详细描述
Total 289 patients were enrolled and randomized in a 1:1 ratio to the group of JS001 (Arm A) with gemcitabine and cisplatin or placebo (Arm B) with gemcitabine and cisplatin every 3 weeks (Q3W) in the 'during chemotherapy' phase. During the 'post-chemotherapy' phase, patients randomized to Arm A or Arm B will continue treatment with JS001 or placebo as maintenance therapy Q3W until excessive toxicity or progressive disease, withdrawal of consent or Investigator's judgement or a maximum of 2 years. Tumor evaluation scans will be performed at screening (as baseline) then every 6weeks in the first 12 months then every 9 weeks thereafter until objective disease progression. The primary objective is to compare PFS as assessed by the IRC in ITT population (all randomized patients).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Age ≥ 18 years and ≤75 years.
- •2. Histological/cytological confirmation of NPC.
- •3. Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment.
- •4. At least 1 measurable lesion according to RECIST version 1.
- •5. Life expectancy ≥ 3 months
排除标准
- •1. History of severe hypersensitivity reactions to other mAbs or any ingredient of JS
- •2. Prior therapy targeting PD-1 receptor, or its ligand PD-L1, or cytotoxic T lymphocyte associated protein 4 (CTLA4) receptor.
- •3. Major surgical procedure other than for diagnosis of NPC within 28 days prior to randomization or anticipation of need for a major surgical procedure during the study
- •4. History of hypersensitivity to gemcitabine or cisplatin or to any of the excipients.
- •5. Female patients who are at pregnancy or lactation.
研究组 & 干预措施
placebo combine with chemotherapy
Gemcitabine 1000 mg/m² IV are given on Days 1 & 8, and cisplatin 80 mg/m² IV are given on Day 1 of each cycle，placebo will be administered at the dose of 240 mg Q3W before that. Chemotherapy is given Q3W for up to 6 cycles and placebo for up to 2 years
干预措施: Placebos (Drug)
TORIPALIMAB INJECTION(JS001 )combine with chemotherapy
Gemcitabine 1000 mg/m² IV are given on Days 1 & 8, and cisplatin 80 mg/m² IV are given on Day 1 of each cycle，JS001 will be administered at the dose of 240 mg Q3W before that. Chemotherapy is given Q3W for up to 6 cycles and JS001 for up to2years
干预措施: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy (Biological)
结局指标
主要结局
IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1
时间窗: up to 2 years
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy as measured by IRC-assessed progression free survival (PFS) according to RECIST v1.1 in all patients. The definition of Progressive Disease: At least a 20% increasein the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. or the appearance of one or more new lesions is also considered progression.
次要结局
- OS(The time frame of OS collected is upto about 48months.)
- Investigator-assessed ORR According to RECIST v1.1(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- Investigator-assessed DoR According to RECIST v1.1(From date of response until progressive disease. Up to 2 approximately years)
- Investigator-assessed DCR According to RECIST v1.1(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- Investigator-assessed PFS According to RECIST v1.1(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- Investigator-assessed PFS Rate at 1 Year(up to approximately 1years)
- OS Rate at 1 Year(Up to approximately 1 years)
- IRC-assessed ORR According to RECIST v1.1(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- IRC-assessed DoR According to RECIST v1.1(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- IRC-assessed DCR According to RECIST v1.1(From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years)
- Number of Participants Experiencing an Adverse Event(AE)(From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years)
- Anti-drug Antibody(ADA)(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- PFS IRC-assessed Per irRECIST(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- ORR IRC-assessed Per irRECIST(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- DoR IRC-assessed Per irRECIST(From date of response until progressive disease. Up to 2 approximately years)
- DCR IRC-assessed Per irRECIST(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- Investigator-assessed PFS Rate at 2 Years(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- OS Rate at 2 Years(Up to approximately 2 years)
- PFS Investigator-assessed Per irRECIST(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- ORR Investigator-assessed Per irRECIST(From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years)
- DoR Investigator-assessed Per irRECIST(From date of response until progressive disease. Up to 2 approximately years)
- DCR Investigator-assessed Per irRECIST(Up to approximately 42 months)