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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent or Metastatic Nasopharyngeal Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Placebo; Drug: Gemcitabin; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China
      • Cancer Hospital Chinese Academy of Medical Science
  • Chongqing
    • Chongqing, Chongqing, China, 404199
      • Chongqing Three Gorges Central Hospital
    • Haikou, Chongqing, China, 570311
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital , Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510059
      • Cancer Center of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510000
      • The first Affiliated Hospital of guangzhou University of traditional chinese medicine - Oncology
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College - Oncology
    • Zhanjiang, Guangdong, China, 524000
      • Affiliated Hospital of Guangdong Medical University
    • Zhongshan, Guangdong, China, 528400
      • People's Hospital of Zhongshan City
    • Zhuhai, Guangdong, China, 519000
      • The Fifth Affiliated Hospital Sun Yat-Sen University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The People's Hospital of Guangxi Zhuang Autonomous Region
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital& Oncology Medical College
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital - Oncology
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital - Oncology
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 400037
      • Hubei Cancer Hospital - Oncology
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410018
      • Changsha Central Hospital
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
      • Affiliated Hospital of Nantong University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital ,Sichuan University
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
• Taiwan
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • NAP
    • Changhua, NAP, Taiwan, 500-06
      • Changhua Christian Hospital
• Thailand
  • Bangkok
    • Dusit, Bangkok, Thailand, 10300
      • Vajira Hospital [SSU]
    • Ratchathewi, Bangkok, Thailand, 10400
      • Ramathibodi Hospital - Mahidol University - Hematology [SSU]
  • Hat Yai
    • Song Phi Nong, Hat Yai, Thailand, 90110
      • Prince of Songkla University [SSU]
  • Muang
    • Chiang Mai, Muang, Thailand, 50200
      • Maharaj Nakorn Chiang Mai Hospital [SSU]
    • Khon Kaen, Muang, Thailand, 40002
      • Khon Kaen University, Srinagarind Hospital [SSU]

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
2. 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)
3. Histologically or cytologically confirmed, recurrent or metastatic NPC
4. 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
5. ECOG performance status ≤ 1
6. Must have ≥ 1 measurable lesions as defined per RECIST v1.1
7. Must be treatment-naive for recurrent or metastatic nasopharyngeal cancer (NPC)

Key Exclusion Criteria:

1. Participants with locally recurrence suitable for curative surgery or radiotherapy

2. 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.

3. 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
4. Received prior therapies targeting PD-1 or PD-L1
5. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
6. Active autoimmune diseases or history of autoimmune diseases that may relapse
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab combined with Gemcitabine Plus Cisplatin; 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; 200 mg administered intravenously (IV); Other Names: BGB-A317; Drug: Gemcitabin; 1 g/m2, administered as an IV infusion within 30 minutes; Drug: Cisplatin; 80 mg/m2, administered as an IV infusion over 4 hours
Placebo Comparator: Placebo combined with Gemcitabine Plus Cisplatin; 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; Placebo to match Tislelizumab; Drug: Gemcitabin; 1 g/m2, administered as an IV infusion within 30 minutes; Drug: Cisplatin; 80 mg/m2, administered as an IV infusion over 4 hours

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Li Zhang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2019
• Primary Completion (Actual): March 26, 2021
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Gemcitabine; Tislelizumab
• Other Study ID Numbers: BGB-A317-309; CTR20182534 (Registry Identifier: Center for drug evaluation, CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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