The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer

Recurrent or Metastatic NPC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03581786
• Other study ID #: JS001-015-III-NPC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 18, 2018
• Est. completion date: October 30, 2022

Study information

• Verified date: August 2021
• Source: Shanghai Junshi Bioscience Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 289
• Est. completion date: October 30, 2022
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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 1.1.
• 5. Life expectancy = 3 months

Exclusion Criteria:

• 1. History of severe hypersensitivity reactions to other mAbs or any ingredient of JS001.
• 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.

Related Conditions & MeSH terms

• Recurrent or Metastatic NPC

Intervention

Biological:
• TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy

Drug:
• Placebos
placebo combine with chemotherapy

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	Affiliated Cancer Hospital & Institute of Guangzhou Medical University	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Guizhou Cancer Hospital_Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Hainan General Hospital (Hainan Province People's Hospital)	Haikou	Hainan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Liuzhou Worker's Hospital	Liuzhou	Guangxi
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangsu Oncology Hospital	Nanjing	Jiangsu
China	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Fudan University Cancer Hospital	Shanghai	Shanghai
China	Shanghai first people's hospital	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangzhou
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Hebei Oncology Hospital	Shijiazhuang	Hebei
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & TechnologyTongji Hospital	Wuhan	Hubei
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangzhou
China	The Fifth Affiliated Hospital Sun Yat-Sen University - Medical Oncology	Zhuhai	Guangzhou
Singapore	National Cancer Centre	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Taiwan	China Medical University Hospital	Taichung City
Taiwan	TaiChung Veterans General Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Junshi Bioscience Co., Ltd.

Countries where clinical trial is conducted

China,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1	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.	up to 2 years
Secondary	OS	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.	up to 5 years
Secondary	Investigator-assessed ORR According to RECIST v1.1	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.	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
Secondary	Investigator-assessed DoR According to RECIST v1.1	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.	From date of response until progressive disease. Up to 2 approximately years
Secondary	Investigator-assessed DCR According to RECIST v1.1	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.	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
Secondary	Investigator-assessed PFS According to RECIST v1.1	To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by Investigators-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
Secondary	Investigator-assessed PFS Rate at 1 and 2 Years	To evaluate the PFS rate at 1 and 2 years in each treatment arm by investigator	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
Secondary	OS Rate at 1 and 2 Years	To evaluate the OS rate at 1 and 2 years in each treatment arm	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
Secondary	Patient-Reported Outcome (PRO) Using EORTC QLQ-C30, EORTC QLQ-H&N35 and ECOG Performance Status Assessments	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	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
Secondary	IRC-assessed ORR According to RECIST v1.1	health related quality of life (HRQoL) in patients treated with JS001 plus chemotherapy compared with placebo plus chemotherapy using the EORTC QLQ-H&N35	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
Secondary	IRC-assessed DoR According to RECIST v1.1	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.	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
Secondary	IRC-assessed DCR According to RECIST v1.1	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.	From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
Secondary	Safety Variables Will be Monitored and Reported:AE.SAE.Vital Signs,Physical Examinations,Laboratory Variable,ECG	Incidence of serious adverse events(SAE) as assessed by CTCAE version 5.0	From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
Secondary	ADAs	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.	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
Secondary	PFS Assessed Per irRECIST	To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to 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
Secondary	ORR Assessed Per irRECIST	To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to 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
Secondary	DoR Assessed Per irRECIST	To evaluate DoR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.	From date of response until progressive disease. Up to 2 approximately years
Secondary	DCR Assessed Per irRECIST	To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to 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