The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer
- Conditions
- Recurrent or Metastatic NPC
- Interventions
- Drug: PlacebosBiological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
- Registration Number
- NCT03581786
- Lead Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 289
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- Age ≥ 18 years and ≤75 years.
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- Histological/cytological confirmation of NPC.
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- 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.
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- At least 1 measurable lesion according to RECIST version 1.1.
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- Life expectancy ≥ 3 months
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- History of severe hypersensitivity reactions to other mAbs or any ingredient of JS001.
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- Prior therapy targeting PD-1 receptor, or its ligand PD-L1, or cytotoxic T lymphocyte associated protein 4 (CTLA4) receptor.
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- 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
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- History of hypersensitivity to gemcitabine or cisplatin or to any of the excipients.
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- Female patients who are at pregnancy or lactation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo combine with chemotherapy Placebos 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 TORIPALIMAB INJECTION(JS001 )combine with chemotherapy 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
- Primary Outcome Measures
Name Time Method IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1 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 (thisincludes the baseline sum if that is the smallest on study). In addition to the relative increase of20%, 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.
- Secondary Outcome Measures
Name Time Method Investigator-assessed DoR According to RECIST v1.1 From date of response until progressive disease. Up to 2 approximately years To evaluate the efficacy of TORIPALIMAB INJECTION(JS001 )plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed duration of response (DoR) according to RECIST v1.1.
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 To evaluate the efficacy of TORIPALIMAB INJECTION(JS001) plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed disease control rate (DCR) according to RECIST v1.1.
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 To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by Investigators-assessed PFS according to RECIST v1.1
Investigator-assessed PFS Rate at 1 and 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 To evaluate the PFS rate at 1 and 2 years in each treatment arm by investigator
OS Rate at 1 and 2 Years From date of randomization until death, loss to follow-up, or study termination by the Sponsor whichever occurs first.Up to 3.5 approximately years To evaluate the OS rate at 1 and 2 years in each treatment arm
Patient-Reported Outcome (PRO) Using EORTC QLQ-C30, EORTC QLQ-H&N35 and ECOG Performance Status Assessments 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 health related quality of life (HRQoL) in patients treated with JS001 plus chemotherapy compared with placebo plus chemotherapy using the EORTC QLQ-C30 \&EORTC QLQ-H\&N35ECOG
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 health related quality of life (HRQoL) in patients treated with JS001 plus chemotherapy compared with placebo plus chemotherapy using the EORTC QLQ-H\&N35
Safety Variables Will be Monitored and Reported:AE.SAE.Vital Signs,Physical Examinations,Laboratory Variable,ECG From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years Incidence of serious adverse events(SAE) as assessed by CTCAE version 5.0
ADAs 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 To evaluate the incidence and titers of ADAs against JS001 and to explore the potential relationship of the immunogenicity response with pharmacodynamics, safety and efficacy.
OS up to 5 years To evaluate the efficacy of TORIPALIMAB INJECTION(JS001 )plus chemotherapy compared with placebo plus chemotherapy, as measured by overall survival (OS).
an AnticipatedReporting Date of final OS in 2023.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 To evaluate the efficacy of TORIPALIMAB INJECTION(JS001) plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1.
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 To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by IRC-assessed duration of response (DoR) according to RECIST v1.1.
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 To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by IRC-assessed disease control rate (DCR) according to RECIST v1.1.
PFS 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 To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.
ORR 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 To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.
DoR Assessed Per irRECIST From date of response until progressive disease. Up to 2 approximately years To evaluate DoR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.
DCR 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 To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.
Trial Locations
- Locations (32)
National Cancer Centre
🇸🇬Singapore, Singapore
China Medical University Hospital
🇨🇳Taichung City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
The People's Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Hainan General Hospital (Hainan Province People's Hospital)
🇨🇳Haikou, Hainan, China
Shenzhen People's Hospital
🇨🇳Shenzhen, Guangdong, China
Jiangsu Oncology Hospital
🇨🇳Nanjing, Jiangsu, China
Affiliated Hospital of Guangdong Medical University
🇨🇳Zhanjiang, Guangzhou, China
Sun Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Liuzhou Worker's Hospital
🇨🇳Liuzhou, Guangxi, China
The Fifth Affiliated Hospital Sun Yat-Sen University - Medical Oncology
🇨🇳Zhuhai, Guangzhou, China
Guizhou Cancer Hospital_Affiliated Hospital of Guizhou Medical University
🇨🇳Guiyang, Guizhou, China
Hebei Oncology Hospital
🇨🇳Shijiazhuang, Hebei, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Fudan University Cancer Hospital
🇨🇳Shanghai, Shanghai, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Shanghai first people's hospital
🇨🇳Shanghai, Shanghai, China
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & TechnologyTongji Hospital
🇨🇳Wuhan, Hubei, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Cancer Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangzhou, China
TaiChung Veterans General Hospital
🇨🇳Taichung City, Taiwan
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China