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

• ClinicalTrials.gov Identifier: NCT03581786
• Recruitment Status: Active, not recruiting
• First Posted: July 10, 2018
• Results First Posted: April 18, 2022
• Last Update Posted: April 18, 2022
• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Information provided by (Responsible Party): Shanghai Junshi Bioscience Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent or Metastatic NPC	Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy; Drug: Placebos	Phase 3

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 289 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 18, 2018
• Actual Primary Completion Date: May 30, 2020
• Estimated Study Completion Date: October 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 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	Drug: Placebos; placebo combine with chemotherapy
Experimental: 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	Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy; TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy

Outcome Measures

Primary Outcome Measures :

1. IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1 [ Time Frame: 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 :

1. OS [ Time Frame: 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.

2. Investigator-assessed ORR According to RECIST v1.1 [ Time Frame: 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.
3. Investigator-assessed DoR According to RECIST v1.1 [ Time Frame: 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.
4. Investigator-assessed DCR According to RECIST v1.1 [ Time Frame: 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.
5. Investigator-assessed PFS According to RECIST v1.1 [ Time Frame: 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
6. Investigator-assessed PFS Rate at 1 and 2 Years [ Time Frame: 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
7. OS Rate at 1 and 2 Years [ Time Frame: 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
8. Patient-Reported Outcome (PRO) Using EORTC QLQ-C30, EORTC QLQ-H&N35 and ECOG Performance Status Assessments [ Time Frame: 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
9. IRC-assessed ORR According to RECIST v1.1 [ Time Frame: 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
10. IRC-assessed DoR According to RECIST v1.1 [ Time Frame: 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.
11. IRC-assessed DCR According to RECIST v1.1 [ Time Frame: 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.
12. Safety Variables Will be Monitored and Reported:AE.SAE.Vital Signs,Physical Examinations,Laboratory Variable,ECG [ Time Frame: 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
13. ADAs [ Time Frame: 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.
14. PFS Assessed Per irRECIST [ Time Frame: 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.
15. ORR Assessed Per irRECIST [ Time Frame: 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.
16. DoR Assessed Per irRECIST [ Time Frame: 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.
17. DCR Assessed Per irRECIST [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing, China, 100021

China, Fujian

Fujian Medical University Union Hospital

Fuzhou, Fujian, China, 350000

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, China, 350000

China, Guangdong

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China, 510060

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Guangzhou, Guangdong, China, 510095

Nanfang Hospital

Guangzhou, Guangdong, China, 510515

Shenzhen People's Hospital

Shenzhen, Guangdong, China, 518020

China, Guangxi

Liuzhou Worker's Hospital

Liuzhou, Guangxi, China, 545000

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, China, 530021

China, Guangzhou

Cancer Hospital of Shantou University Medical College

Shantou, Guangzhou, China, 515031

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangzhou, China, 130012

The Fifth Affiliated Hospital Sun Yat-Sen University - Medical Oncology

Zhuhai, Guangzhou, China, 519000

China, Guizhou

Guizhou Cancer Hospital_Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China, 550000

China, Hainan

Hainan General Hospital (Hainan Province People's Hospital)

Haikou, Hainan, China, 570311

China, Hebei

Hebei Oncology Hospital

Shijiazhuang, Hebei, China, 50011

China, Hubei

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China, 430023

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & TechnologyTongji Hospital

Wuhan, Hubei, China, 430030

China, Hunan

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China, 410011

Hunan Cancer Hospital

Changsha, Hunan, China, 410013

China, Jiangsu

Jiangsu Oncology Hospital

Nanjing, Jiangsu, China, 210000

China, Jiangxi

Jiangxi Cancer Hospital

Nanchang, Jiangxi, China, 330029

China, Shanghai

Fudan University Cancer Hospital

Shanghai, Shanghai, China, 200032

Shanghai first people's hospital

Shanghai, Shanghai, China, 200080

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China, 610041

China, Zhejiang

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

Singapore

National Cancer Centre

Singapore, Singapore, 169610

Tan Tock Seng Hospital

Singapore, Singapore, 308433

Taiwan

China Medical University Hospital

Taichung City, Taiwan, 404

TaiChung Veterans General Hospital

Taichung City, Taiwan, 40705

National Cheng Kung University Hospital

Tainan, Taiwan, 704

Taipei Veterans General Hospital

Taipei, Taiwan, 112

Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital

Taoyuan, Taiwan, 333

Sponsors and Collaborators

Shanghai Junshi Bioscience Co., Ltd.

Investigators

• Principal Investigator: Ruihua Xu, Ph.D; Sun Yat-sen University

  Study Documents (Full-Text)

Documents provided by Shanghai Junshi Bioscience Co., Ltd.:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] October 14, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2. Erratum In: Nat Med. 2022 Jan;28(1):214.

• Responsible Party: Shanghai Junshi Bioscience Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03581786
• Other Study ID Numbers: JS001-015-III-NPC
• First Posted: July 10, 2018
• Results First Posted: April 18, 2022
• Last Update Posted: April 18, 2022
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Recurrence; Disease Attributes; Pathologic Processes