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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Recurrent or Metastatic NPC

Intervention / Treatment
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* Biological: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo combine with chemotherapy<br>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<br>* placebo combine with chemotherapy<br>|
| Experimental: TORIPALIMAB INJECTION(JS001 )combine with chemotherapy<br>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<br>* TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy<br>|

What is the study measuring?
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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 |