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Phase III Study of Comparing TORIPALIMAB INJECTION Versus Placebo Combined With Chemotherapy for Recurrent or Metastatic Nasophapyngeal Cancer

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ClinicalTrials.gov Identifier: NCT03581786
Recruitment Status : Completed
First Posted : July 10, 2018
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
Shanghai Junshi Bioscience Co., Ltd.

Tracking Information
First Submitted Date  ICMJE June 5, 2018
First Posted Date  ICMJE July 10, 2018
Last Update Posted Date January 25, 2021
Actual Study Start Date  ICMJE October 18, 2018
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
PFS [ Time Frame: up to 2 years ]
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy,as measured by investigator-assessed progression free survival (PFS) according to RECIST v1.1 in all patients.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2021)
  • 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).
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • OS [ Time Frame: up to 5 years ]
    To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by overall survival (OS).
  • ORR [ 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 investigator-assessed overall response rate (ORR) according to RECIST v1.1.
  • DOR [ Time Frame: From date of response until progressive disease. Up to 2 approximately years ]
    To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed duration of response (DoR) according to RECIST v1.1.
  • DCR [ 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 investigator-assessed disease control rate (DCR) according to RECIST v1.1.
  • iDMC-assessed PFS [ 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 an independent monitoring committee (iDMC)-assessed PFS according to RECIST v1.1
  • PFS rate [ 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
  • OS rate [ 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
  • Patient-Reported Outcomes collected via the EORTC QLQ-C30 [ 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
  • Patient-Reported Outcomes collected via the EORTC QLQ-H&N35 [ 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
  • health related quality of life using ECOG performance status [ 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 ECOG performance status assessments
  • Incidence and severity of adverse events as assessed by CTCAE version 5.0 [ Time Frame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years ]
    Incidence and severity of adverse events as assessed by CTCAE version 5.0
  • Incidence of serious adverse events(SAE) as assessed by CTCAE version 5.0 [ 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Study of Comparing TORIPALIMAB INJECTION Versus Placebo Combined With Chemotherapy for Recurrent or Metastatic Nasophapyngeal Cancer
Official Title  ICMJE 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
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Recurrent or Metastatic NPC
Intervention  ICMJE
  • Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
    TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
  • Drug: Placebos
    placebo combine with chemotherapy
Study Arms  ICMJE
  • Placebo Comparator: placebo combine with chemotherapy
    Intervention: Drug: Placebos
  • Experimental: TORIPALIMAB INJECTION(JS001 )combine with chemotherapy
    Intervention: Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2020)
289
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2018)
280
Actual Study Completion Date  ICMJE October 30, 2020
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China,   Singapore,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03581786
Other Study ID Numbers  ICMJE JS001-015-III-NPC
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shanghai Junshi Bioscience Co., Ltd.
Study Sponsor  ICMJE Shanghai Junshi Bioscience Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Shanghai Junshi Bioscience Co., Ltd.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP