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

NCT03924986 | Completed Phase 3 Results DMC

• 2 other identifiers: BGB-A317-309CTR20182534
• Study Type: interventional
• Target: 263
• Locations: 3 countries
• Sites: 37

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.

Conditions

Recurrent or Metastatic Nasopharyngeal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival as Assessed by the Independent Review Committee (IRC)

  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.

  Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months)

Secondary Outcomes (8)

• 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)

Study Arms (2)

Arm A: Tislelizumab + Gemcitabine + Cisplatin

EXPERIMENTAL

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.

Drug: Tislelizumab; Drug: Gemcitabine; Drug: Cisplatin

Arm B: Placebo + Gemcitabine + Cisplatin

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Tislelizumab DRUG

200 mg intravenously (IV) once every 3 weeks (Q3W)

Also known as: BGB-A317

Arm A: Tislelizumab + Gemcitabine + Cisplatin

Placebo DRUG

Placebo to match tislelizumab (administered intravenously Q3W)

Arm B: Placebo + Gemcitabine + Cisplatin

Gemcitabine DRUG

1 gram per square meter of body surface area (g/m\^2) on Day 1 and day 8 of each cycle, administered as an IV infusion within 30 minutes, for 4 to 6 cycles

Arm A: Tislelizumab + Gemcitabine + Cisplatin; Arm B: Placebo + Gemcitabine + Cisplatin

Cisplatin DRUG

80 milligrams per square meter of body surface area (mg/m\^2) on Day 1 of each cycle, administered as an IV infusion for over 4 hours if possible or with proper infusion time based on local clinical guidelines or clinical practice and according to the treating physician's clinical judgment, for 4 to 6 cycles.

Arm A: Tislelizumab + Gemcitabine + Cisplatin; Arm B: Placebo + Gemcitabine + Cisplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• BeiGene: lead

Study Sites (37)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

Location

Chongqing Three Gorges Central Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

Location

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)

Guangzhou, Guangdong, 510000, China

Location

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, 510030, China

Location

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

Guangzhou, Guangdong, 510405, China

Location

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, 515031, China

Location

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, 524000, China

Location

The Peoples Hospital of Zhongshan City

Zhongshan, Guangdong, 528403, China

Location

The Fifth Affiliated Hospital Sun Yat Sen University

Zhuhai, Guangdong, 519000, China

Location

The Peoples Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, 530021, China

Location

The Tumor Hospital Affiliated to Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

Hainan General Hospital

Haikou, Hainan, 570206, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Changsha Central Hospital

Changsha, Hunan, 410004, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

Affiliated Hospital of Nantong University

Nantong, Jiangsu, 201203, China

Location

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

Sichuan Cancer Hospital and Institute

Chengdu, Sichuan, 610041, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Changhua Christian Hospital

Changhua, 50006, Taiwan

Location

Veterans General Hospital Taichung

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Ramathibodi Hospital Mahidol University Hematology

Bangkok, 10400, Thailand

Location

Songklanagarind Hospital (Prince of Songkhla University)

Hat Yai, 90110, Thailand

Location

Srinagarind Hospital (Khon Kaen University)

Muang, 40002, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital (Chiang Mai University)

Muang, 50200, Thailand

Location

Related Publications (3)

• Zhang L, Liu T, Wang H, Shi S, Yang Y. A Phase 3 Trial in Progress Comparing Tislelizumab Plus Chemotherapy With Placebo Plus Chemotherapy in Chinese Patients With Recurrent or Metastatic Nasopharyngeal Cancer. Abstract published at: 22nd Annual Meeting of the Chinese Society of Clinical Oncology; September, 2019; Xiamen, China.

  BACKGROUND

• Yang Y, Pan J, Chen N, Guo Y, Huang X, Wu Y, Leaw S, Bai F, Wang Y, Zhao N, Tang B, Barnes G. Effects of tislelizumab on health-related quality of life in patients with recurrent or metastatic nasopharyngeal cancer. Head Neck. 2024 Sep;46(9):2301-2314. doi: 10.1002/hed.27785. Epub 2024 Apr 26.

  PMID: 38671587 DERIVED

• Yang Y, Pan J, Wang H, Zhao Y, Qu S, Chen N, Chen X, Sun Y, He X, Hu C, Lin L, Yu Q, Wang S, Wang G, Lei F, Wen J, Yang K, Lin Z, Guo Y, Chen S, Huang X, Wu Y, Liang L, Chen C, Bai F, Ma X, Zhang Y, Leaw S, Zhang L, Fang W. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). Cancer Cell. 2023 Jun 12;41(6):1061-1072.e4. doi: 10.1016/j.ccell.2023.04.014. Epub 2023 May 18.

  PMID: 37207654 DERIVED

MeSH Terms

Conditions

Recurrence; Nasopharyngeal Neoplasms

Interventions

tislelizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

1-877-828-5568

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: April 23, 2019
• Study Start: March 27, 2019
• Primary Completion: March 26, 2021
• Study Completion: December 8, 2023
• Last Updated: January 31, 2025
• Results First Posted: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (30); TW (3); TH (4)