Tislelizumab Combined With Chemotherapy Versus Chemotherapy Alone in Recurrent or Metastatic Nasopharyngeal Cancer

Study Overview
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Brief Summary
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This is a Phase 3, Multicenter, Double-Blind, Randomized, Placebo-controlled Study to Compare the Efficacy and Safety of Tislelizumab (BGB-A317) Combined With Gemcitabine Plus Cisplatin Versus Placebo Combined With Gemcitabine Plus Cisplatin as First Line Treatment for Recurrent or Metastatic Nasopharyngeal Cancer.

Official Title
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Phase 3, Double-Blind, Randomized Study to Compare the Efficacy and Safety of Tislelizumab Combined With Chemotherapy Versus Chemotherapy as First-Line Treatment for Recurrent or Metastatic Nasopharyngeal Cancer

Conditions
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Recurrent or Metastatic Nasopharyngeal Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Placebo
* Drug: Gemcitabin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments Aged between 18 to 75 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place) Histologically or cytologically confirmed, recurrent or metastatic NPC Participants must be able to provide fresh or archival tumor tissues (FFPE blocks or approximately 10 [≥ 6] freshly cut unstained FFPE slides) with an associated pathological report. The archival tumor tissues must be collected within 2 years before screening. In the absence of sufficient archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is mandatory ECOG performance status ≤ 1 Must have ≥ 1 measurable lesions as defined per RECIST v1.1 Must be treatment-naive for recurrent or metastatic nasopharyngeal cancer (NPC) Key Exclusion Criteria: Participants with locally recurrence suitable for curative surgery or radiotherapy Received any approved systemic anticancer therapy, including hormonal therapy, within 28 days prior to initiation of study treatment. The following exception is allowed: -Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging. Has received any immunotherapy (including but not limited to interferons, interleukin 2, tumor necrosis factor interleukin, and thymoxin) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) of randomization Received prior therapies targeting PD-1 or PD-L1 Active leptomeningeal disease or uncontrolled, untreated brain metastasis Active autoimmune diseases or history of autoimmune diseases that may relapse Any active malignancy ≤ 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast) NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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 |
| --- | --- |
| Experimental: Tislelizumab combined with Gemcitabine Plus Cisplatin<br>Tislelizumab will be administered once every 3 weeks (Q3W) Gemcitabine on Day 1, Day 8 of each 3 week cycle, for 4 to 6 cycles Cisplatin on Day 1 of each 3 week cycle, for 4 to 6 cycles | Drug: Tislelizumab<br>* 200 mg administered intravenously (IV)<br>* Other names: BGB-A317;Drug: Gemcitabin<br>* 1 g/m2, administered as an IV infusion within 30 minutes<br>Drug: Cisplatin<br>* 80 mg/m2, administered as an IV infusion over 4 hours<br>|
| Placebo Comparator: Placebo combined with Gemcitabine Plus Cisplatin<br>Placebo will be administered once every 3 weeks (Q3W) Gemcitabine on Day 1, Day 8 of 3 week each cycle, for 4 to 6 cycles Cisplatin on Day 1 of 3 week each cycle, for 4 to 6 cycles | Drug: Placebo<br>* Placebo to match Tislelizumab<br>Drug: Gemcitabin<br>* 1 g/m2, administered as an IV infusion within 30 minutes<br>Drug: Cisplatin<br>* 80 mg/m2, administered as an IV infusion over 4 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival as assessed by the Independent Review Committee: the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurs first, as assessed by the Independent Review Committee per RECIST v1.1 in an Intent-to-Treat analysis set. | up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The time from the date of randomization to the date of death due to any cause in an Intent-to-Treat analysis set. | up to 2 years. | 
| Duration of response | Duration of response as assessed by the Independent Review Committee: the time from the first occurrence of a documented objective response to the time of relapse, or death from any cause, whichever comes first, as assessed by the Independent Review Committee per RECIST v1.1 in all randomized participants with documented objective responses. | up to 2 years. | 
| Overall response rate | Overall response rate as assessed by the Independent Review Committee: the proportion of participants who had complete response or partial response as assessed by the Independent Review Committee per RECIST v1.1 in all randomized participants with measurable disease at baseline. | up to 2 years. | 
| Progression-free survival as assessed by the investigator | The time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurs first, as assessed by the investigator per RECIST v1.1 in an Intent-to-Treat analysis set. | up to 2 years. | 
| Progression-free survival after next line of treatment as assessed by the investigator | The time from randomization to second/subsequent disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurs first. | up to 2 years. |