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Recurrent or Metastatic Nasopharyngeal CancerPhase 3RATIONALE-309NCT03924986

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

A Phase 3 study testing Tislelizumab, Gemcitabine and Cisplatin in people with Recurrent or Metastatic Nasopharyngeal Cancer, run by BeiGene at 37 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Tislelizumab, Gemcitabine and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
263 participants
Where
37 sitesin 3 countries
Study dates
27 Mar 2019to 8 Dec 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

37 sites in 3 countries.

37 sites in 3 countries

China30 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Changsha Central Hospital

    Changsha, Hunan, 410004

  • Hunan Cancer Hospital

    Changsha, Hunan, 410013

  • Sichuan Cancer Hospital and Institute

    Chengdu, Sichuan, 610041

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

  • Chongqing Cancer Hospital

    Chongqing, Chongqing Municipality, 400030

  • Chongqing Three Gorges Central Hospital

    Chongqing, Chongqing Municipality, 404000

  • Fujian Cancer Hospital

    Fuzhou, Fujian, 350014

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

    Guangzhou, Guangdong, 510000

  • Cancer Center of Guangzhou Medical University

    Guangzhou, Guangdong, 510030

  • Sun Yat Sen University Cancer Center

    Guangzhou, Guangdong, 510060

  • Guangdong Provincial Peoples Hospital

    Guangzhou, Guangdong, 510080

  • The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

    Guangzhou, Guangdong, 510405

  • Hainan General Hospital

    Haikou, Hainan, 570206

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Anhui Provincial Hospital

    Hefei, Anhui, 230000

  • The First Affiliated Hospital of Nanchang University Branch Donghu

    Nanchang, Jiangxi, 330006

  • The Peoples Hospital of Guangxi Zhuang Autonomous Region

    Nanning, Guangxi, 530021

  • The Tumor Hospital Affiliated to Guangxi Medical University

    Nanning, Guangxi, 530021

  • Affiliated Hospital of Nantong University

    Nantong, Jiangsu, 201203

  • Affiliated Zhongshan Hospital of Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Shanghai East Hospital

    Shanghai, Shanghai Municipality, 200120

  • Cancer Hospital of Shantou University Medical College

    Shantou, Guangdong, 515031

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

    Wuhan, Hubei, 430022

  • Hubei Cancer Hospital

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

  • Affiliated Hospital of Guangdong Medical University

    Zhanjiang, Guangdong, 524000

  • The Peoples Hospital of Zhongshan City

    Zhongshan, Guangdong, 528403

  • The Fifth Affiliated Hospital Sun Yat Sen University

    Zhuhai, Guangdong, 519000

Other trials in China

Thailand4 sites

  • Ramathibodi Hospital Mahidol University Hematology

    Bangkok, 10400

  • Songklanagarind Hospital (Prince of Songkhla University)

    Hat Yai, 90110

  • Srinagarind Hospital (Khon Kaen University)

    Muang, 40002

  • Maharaj Nakorn Chiang Mai Hospital (Chiang Mai University)

    Muang, 50200

Other trials in Thailand

Taiwan3 sites

  • Changhua Christian Hospital

    Changhua, 50006

  • Veterans General Hospital Taichung

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, 704

Other trials in Taiwan

About this study

Official title: 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

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.

Being tested
Tislelizumab, Placebo, Gemcitabine, Cisplatin
Medical subject headings
Recurrence, Nasopharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TislelizumabDrug

    Also called BGB-A317

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

  • PlaceboDrug

    Placebo to match tislelizumab (administered intravenously Q3W)

  • GemcitabineDrug

    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

  • CisplatinDrug

    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.

Study groups in NCT03924986
Study groupRoleWhat they receive
Arm A: Tislelizumab + Gemcitabine + CisplatinExperimentalParticipants 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.
Receives: Drug: Tislelizumab; Drug: Gemcitabine; Drug: Cisplatin
Arm B: Placebo + Gemcitabine + CisplatinPlacebo comparatorParticipants 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.
Receives: Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

  1. Overall Response Rate (ORR) as Assessed by the IRC

    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.

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

  2. Duration of Response (DOR) as Assessed by the IRC

    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.

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

  3. Overall Survival (OS) as Assessed by the IRC

    Defined as the time from the date of randomization to the date of death due to any cause.

    Measured: 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)

  4. PFS as Assessed by the Investigator

    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.

    Measured: Through the interim analysis data cut-off date of March 26th, 2021 (up to approximately 23 months)

  5. Progression-free Survival After Next Line of Treatment (PFS2) as Assessed by the Investigator

    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.

    Measured: Through the study completion data cut-off date of December 8th, 2023 (maximum time on study follow-up was 53 months)

  6. 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

    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.

    Measured: Baseline to Cycle 6 (Each cycle is 21 days)

  7. 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

    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.

    Measured: Baseline to Cycle 6 (Each cycle is 21 days)

  8. Number of Participants With Adverse Events

    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.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2019
  2. Study start27 Mar 2019
  3. Primary completion26 Mar 2021
  4. Study completion8 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
263 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03924986
Sponsor's protocol ID
BGB-A317-309
Other IDs
CTR20182534
Acronym
RATIONALE-309
Status last verified
Jan 2025
First submitted
21 Mar 2019
Last updated
31 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • 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.

  • Yang Y, Yen CJ, Pan J, Wang H, Qu S, Chen N, Chen X, Sun Y, He X, Hu C, Lin L, Wu Y, Yuan S, Chen C, Xu X, Ma X, Leaw S, Zhang L, Fang W. First-Line Tislelizumab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer: Three-Year Follow-Up of the Phase 3 RATIONALE-309 Randomized Clinical Trial. JAMA Oncol. 2026 Apr 1;12(4):384-393. doi: 10.1001/jamaoncol.2026.0020.

    PubMed 41746630

  • 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.

    PubMed 38671587

  • 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.

    PubMed 37207654

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tislelizumab, Gemcitabine and Cisplatin in people with Recurrent or Metastatic Nasopharyngeal Cancer, run by BeiGene at 37 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in China, Thailand, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03924986, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.

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