Trial Outcomes & Findings for Tislelizumab Combined With Chemotherapy Versus Chemotherapy Alone in Recurrent or Metastatic Nasopharyngeal Cancer (NPC) (NCT NCT03924986)

Last Updated: 2025-01-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

263 participants

Primary outcome timeframe

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

Results posted on

2025-01-31

Participant Flow

Participants were enrolled in multiple study centers in China, Thailand, and Taiwan. The first participant was consented on March 27th 2019, and the last participant completed on December 8th 2023.

Participant milestones

Participant milestones
Measure	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.	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 disease progression confirmed by the Independent Review Committee (IRC) may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy.
Overall Study STARTED	131	132
Overall Study Treated	131	132
Overall Study Crossed Over to Tislelizumab	0	70
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	131	132

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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 disease progression confirmed by the Independent Review Committee (IRC) may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy.
Overall Study Death	57	66
Overall Study Study Concluded by Sponsor	51	41
Overall Study Withdrawal by Subject	15	20
Overall Study Lost to Follow-up	7	5
Overall Study Miscellaneous	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.	Total n=263 Participants Total of all reporting groups
Age, Continuous	49.0 years STANDARD_DEVIATION 10.62 • n=131 Participants	49.5 years STANDARD_DEVIATION 10.76 • n=132 Participants	49.3 years STANDARD_DEVIATION 10.67 • n=263 Participants
Sex: Female, Male Female	28 Participants n=131 Participants	29 Participants n=132 Participants	57 Participants n=263 Participants
Sex: Female, Male Male	103 Participants n=131 Participants	103 Participants n=132 Participants	206 Participants n=263 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment China	122 participants n=131 Participants	126 participants n=132 Participants	248 participants n=263 Participants
Region of Enrollment Thailand	5 participants n=131 Participants	1 participants n=132 Participants	6 participants n=263 Participants
Region of Enrollment Taiwan	4 participants n=131 Participants	5 participants n=132 Participants	9 participants n=263 Participants
Baseline Target Lesions Sum of Diameters Assessed by Investigator (mm)	65.49 Millimeters (mm) STANDARD_DEVIATION 49.004 • n=131 Participants	57.56 Millimeters (mm) STANDARD_DEVIATION 40.389 • n=132 Participants	61.51 Millimeters (mm) STANDARD_DEVIATION 44.978 • n=263 Participants

PRIMARY outcome

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

Population: ITT analysis set

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.
Progression-free Survival as Assessed by the Independent Review Committee (IRC)	9.2 Months Interval 7.6 to 10.1	7.4 Months Interval 5.6 to 7.5

SECONDARY outcome

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

Population: ITT analysis set

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.
Overall Response Rate (ORR) as Assessed by the IRC	69.5 percentage of participants Interval 60.8 to 77.2	55.3 percentage of participants Interval 46.4 to 64.0

SECONDARY outcome

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

Population: ITT analysis Set. Only participants with best overall response of complete response or partial response confirmed per RECIST v1.1 were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=91 Participants 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 n=73 Participants 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.
Duration of Response (DOR) as Assessed by the IRC	8.5 months Interval 6.5 to Not estimable due to insufficient number of participants with events	6.1 months Interval 4.7 to 6.2

SECONDARY outcome

Timeframe: 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)

Population: ITT analysis set

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

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.
Overall Survival (OS) as Assessed by the IRC	45.3 Months Interval 33.4 to Not estimable due to insufficient number of participants with events	31.8 Months Interval 25.0 to Not estimable due to insufficient number of participants with events

SECONDARY outcome

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

Population: ITT analysis set

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.
PFS as Assessed by the Investigator	9.8 months Interval 7.8 to 11.9	7.6 months Interval 6.6 to 7.8

SECONDARY outcome

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

Population: ITT analysis set

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=131 Participants 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 n=132 Participants 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.
Progression-free Survival After Next Line of Treatment (PFS2) as Assessed by the Investigator	45.3 months Interval 31.5 to Not estimable due to insufficient number of participants with events	20.5 months Interval 13.9 to 27.2

SECONDARY outcome

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

Population: The HRQoL analysis set includes all randomized participants who received any dose of study drug and completed at least one HRQoL assessment. Only participants with data at both baseline and the each postbaseline visit are included in the summary statistics for change from baseline.

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=108 Participants 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 n=104 Participants 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.
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	0.2 score on a scale Standard Deviation 25.18	-0.1 score on a scale Standard Deviation 20.72

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=108 Participants 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 n=104 Participants 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.
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	-0.3 score on a scale Standard Deviation 6.40	-0.3 score on a scale Standard Deviation 7.17

SECONDARY outcome

Timeframe: 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).

Population: The Safety analysis set includes all randomized participants who received any dose of any component of study drug. Two participants randomized to Arm B who received 100 mg tislelizumab in error were analyzed as part of Arm A for the Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Arm A: Tislelizumab + Gemcitabine + Cisplatin n=133 Participants 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 n=130 Participants 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.
Number of Participants With Adverse Events TEAEs	133 Participants	129 Participants
Number of Participants With Adverse Events SAEs	47 Participants	46 Participants

Adverse Events

Arm A: Tislelizumab + Gemcitabine + Cisplatin

Serious events: 47 serious events

Other events: 133 other events

Deaths: 57 deaths

Arm B: Placebo + Gemcitabine + Cisplatin

Serious events: 46 serious events

Other events: 129 other events

Deaths: 31 deaths

Post Crossover Tislelizumab

Serious events: 15 serious events

Other events: 60 other events

Deaths: 35 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: 1-877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER