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
Overview
- Phase
- Phase 3
- Intervention
- Tislelizumab
- Conditions
- Recurrent or Metastatic Nasopharyngeal Cancer
- Sponsor
- BeiGene
- Enrollment
- 263
- Locations
- 37
- Primary Endpoint
- Progression-free Survival as Assessed by the Independent Review Committee (IRC)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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 (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.
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 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.
Arms & Interventions
Arm A: Tislelizumab + Gemcitabine + 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.
Intervention: Tislelizumab
Arm A: Tislelizumab + Gemcitabine + 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.
Intervention: Gemcitabine
Arm A: Tislelizumab + Gemcitabine + 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.
Intervention: Cisplatin
Arm B: Placebo + Gemcitabine + 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.
Intervention: Placebo
Arm B: Placebo + Gemcitabine + 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.
Intervention: Gemcitabine
Arm B: Placebo + Gemcitabine + 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.
Intervention: Cisplatin
Outcomes
Primary Outcomes
Progression-free Survival as Assessed by the Independent Review Committee (IRC)
Time Frame: 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 Outcomes
- 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))
- 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))
- 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))
- PFS as Assessed by the Investigator(Through the interim analysis data cut-off date of March 26th, 2021 (up to approximately 23 months))
- 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))
- 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 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))
- 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).)