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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent or Metastatic NPC
• Intervention / Treatment: Drug: Placebos; Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy

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 Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital, Chinese Academy of Medical Sciences
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Medical University Union Hospital
    • Fuzhou, Fujian, China, 350000
      • Fujian Provincial Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510095
      • Affiliated Cancer Hospital & Institute of Guangzhou Medical University
    • Shenzhen, Guangdong, China, 518020
      • ShenZhen People's Hospital
  • Guangxi
    • Liuzhou, Guangxi, China, 545000
      • Liuzhou Worker's Hospital
    • Nanning, Guangxi, China, 530021
      • The people's hospital of Guangxi Zhuang Autonomous Region
  • Guangzhou
    • Shantou, Guangzhou, China, 515031
      • Cancer Hospital of Shantou University Medical College
    • Zhanjiang, Guangzhou, China, 130012
      • Affiliated Hospital of Guangdong Medical University
    • Zhuhai, Guangzhou, China, 519000
      • The Fifth Affiliated Hospital Sun Yat-Sen University - Medical Oncology
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Cancer Hospital_Affiliated Hospital of Guizhou Medical University
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital (Hainan Province People's Hospital)
  • Hebei
    • Shijiazhuang, Hebei, China, 50011
      • Hebei Oncology Hospital
  • Hubei
    • Wuhan, Hubei, China, 430023
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & TechnologyTongji Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Oncology Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Cancer Hospital
    • Shanghai, Shanghai, China, 200080
      • Shanghai First People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer hospital
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
• Taiwan
  • Taichung City, Taiwan, 404
    • China Medical University Hospital
  • Taichung City, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Ruihua Xu, Ph.D, Sun Yat-sen University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2018
• Primary Completion (ACTUAL): May 30, 2020
• Study Completion (ANTICIPATED): October 30, 2022

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (ACTUAL): July 10, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 15, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: JS001-015-III-NPC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No