Tislelizumab Combined With Chemotherapy Versus Chemotherapy Alone in Recurrent or Metastatic Nasopharyngeal Cancer (NPC)
- Conditions
- Recurrent or Metastatic Nasopharyngeal Cancer
- Interventions
- Registration Number
- NCT03924986
- Lead Sponsor
- BeiGene
- Brief Summary
This study was designed 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 263
- 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 (formalin-fixed paraffin-embedded [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
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Must have ≥ 1 measurable lesions as defined per RECIST v1.1
- Must be treatment-naive for recurrent or metastatic NPC.
Key
-
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 programmed cell death protein-1 (PD-1) or programmed cell death protein ligand-1 (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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tislelizumab + Gemcitabine + Cisplatin Tislelizumab Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks (Q3W), gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have continued to receive tislelizumab monotherapy. Arm A: Tislelizumab + Gemcitabine + Cisplatin Gemcitabine Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks (Q3W), gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have continued to receive tislelizumab monotherapy. Arm A: Tislelizumab + Gemcitabine + Cisplatin Cisplatin Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks (Q3W), gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have continued to receive tislelizumab monotherapy. Arm B: Placebo + Gemcitabine + Cisplatin Placebo Participants received placebo IV once every 3 weeks, gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy. Arm B: Placebo + Gemcitabine + Cisplatin Gemcitabine Participants received placebo IV once every 3 weeks, gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy. Arm B: Placebo + Gemcitabine + Cisplatin Cisplatin Participants received placebo IV once every 3 weeks, gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy.
- Primary Outcome Measures
Name Time Method Progression-free Survival as Assessed by the Independent Review Committee (IRC) Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months) Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Kaplan-Meier methodology was used to estimate the median PFS.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) as Assessed by the IRC Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months) Defined as the percentage of participants who had complete response or partial response as assessed by the IRC per RECIST v1.1 in all randomized participants with measurable disease at Baseline.
Duration of Response (DOR) as Assessed by the IRC Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months) Defined as the time from the first occurrence of a documented objective response to the time of relapse, or death from any cause, whichever occurred first, as assessed by the IRC per RECIST v1.1 in all randomized participants with documented objective responses.
Overall Survival (OS) as Assessed by the IRC Through study completion data cut-off date of December 8th, 2023 or last available date showing participants alive (maximum time on study follow-up was 53 months) Defined as the time from the date of randomization to the date of death due to any cause.
PFS as Assessed by the Investigator Through the interim analysis data cut-off date of March 26th, 2021 (up to approximately 23 months) Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1.
Progression-free Survival After Next Line of Treatment (PFS2) as Assessed by the Investigator Through the study completion data cut-off date of December 8th, 2023 (maximum time on study follow-up was 53 months) Defined as the time from randomization to second/subsequent disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status Baseline to Cycle 6 (Each cycle is 21 days) Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-351 (EORTC QLQ-H&N35) Index Score Baseline to Cycle 6 (Each cycle is 21 days) The QLQ-H\&N35 consists of thirty-five questions that are associated with eighteen symptom scales (pain, swallowing, senses, speech, social eating, social contact, sexuality, problem with teeth, problem opening mouth, dry mouth, problem with sense smell, cough, felt ill, pain med, nutritional supplements, feeding tube, weight loss and weight gain).. Raw scores are transformed into a 0 to 100 scale via linear transformation. The index score is calculated as an average of the 18 symptom scales. A negative change from baseline score indicates improvement in symptoms.
Number of Participants With Adverse Events From first dose to 30 days after last dose or new anticancer therapy, or until Dec 8, 2023 data cut-off; max treatment duration: 231 weeks (Arm A), 202 weeks (Arm B). Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, vital signs, electrocardiograms (ECGs), and physical examinations (PEs ), graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. For Arm B, only adverse events reported prior to participants crossing over to receive tislelizumab monotherapy are included.
Trial Locations
- Locations (37)
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
🇨🇳Guangzhou, Guangdong, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
🇨🇳Guangzhou, Guangdong, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
The Peoples Hospital of Zhongshan City
🇨🇳Zhongshan, Guangdong, China
The Fifth Affiliated Hospital Sun Yat Sen University
🇨🇳Zhuhai, Guangdong, China
The Peoples Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
The Tumor Hospital Affiliated to Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Affiliated Hospital of Nantong University
🇨🇳Nantong, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Sichuan Cancer Hospital and Institute
🇨🇳Chengdu, Sichuan, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Veterans General Hospital Taichung
🇨🇳Taichung, Taiwan
Ramathibodi Hospital Mahidol University Hematology
🇹🇭Bangkok, Thailand
Songklanagarind Hospital (Prince of Songkhla University)
🇹🇭Hat Yai, Thailand
Srinagarind Hospital (Khon Kaen University)
🇹🇭Muang, Thailand
Maharaj Nakorn Chiang Mai Hospital (Chiang Mai University)
🇹🇭Muang, Thailand
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Chongqing Three Gorges Central Hospital
🇨🇳Chongqing, Chongqing, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Affiliated Hospital of Guangdong Medical University
🇨🇳Zhanjiang, Guangdong, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Changsha Central Hospital
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan