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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03745222




Registration number
NCT03745222
Ethics application status
Date submitted
9/11/2018
Date registered
19/11/2018
Date last updated
15/07/2020

Titles & IDs
Public title
A Study of Tislelizumab (BGB-A317) Plus Chemoradiotherapy Followed by Tislelizumab Monotherapy in Newly Diagnosed, Stage III Subjects With Locally Advanced, Unresectable Non-small Cell Lung Cancer
Scientific title
A PHASE 3, RANDOMIZED, BLINDED, PLACEBO-CONTROLLED STUDY OF TISLELIZUMAB (BGB-A317) PLUS CHEMORADIOTHERAPY FOLLOWED BY TISLELIZUMAB MONOTHERAPY IN NEWLY DIAGNOSED, STAGE III SUBJECTS WITH LOCALLY ADVANCED, UNRESECTABLE NON-SMALL CELL LUNG CANCER
Secondary ID [1] 0 0
U1111-1216-4294
Secondary ID [2] 0 0
BGB-A317-NSCL-001
Universal Trial Number (UTN)
Trial acronym
RATIONALE001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tislelizumab
Treatment: Drugs - Concurrent chemoradiotherapy (cCRT)
Other interventions - Placebo

Experimental: Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy - Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide

Experimental: Arm 2: Placebo + cCRT followed by tislelizumab monotherapy - Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.

Placebo comparator: Arm 3: Placebo + cCRT followed by placebo monotherapy - Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.


Treatment: Drugs: Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)

Treatment: Drugs: Concurrent chemoradiotherapy (cCRT)
Chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide per standard of care. Radiotherapy will also be given concurrently with chemotherapy.

Other interventions: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 5 years; date of randomization to date of death from any cause.
Secondary outcome [2] 0 0
Overall Survival at 24 Months
Timepoint [2] 0 0
Up to approximately 24 months
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Percentage of Participants Alive and Progression-Free at 12 Months (APF12)
Timepoint [5] 0 0
Up to 12 months
Secondary outcome [6] 0 0
Percentage of Participants Alive and Progression-free at 18 Months (APF18)
Timepoint [6] 0 0
Up to approximately 18 months
Secondary outcome [7] 0 0
Time to Distant Metastasis (TTDM)
Timepoint [7] 0 0
Up to approximately 5 years
Secondary outcome [8] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [8] 0 0
From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days.
Secondary outcome [9] 0 0
Number of Participants With Lung Cancer Symptoms Assessed by the Corresponding Domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and Lung-Cancer Specific QLQ-LC13
Timepoint [9] 0 0
Up to approximately 5 years
Secondary outcome [10] 0 0
Percentage of Participants Who Would Have Continued on to Monotherapy Phase
Timepoint [10] 0 0
Up to approximately 5 years

Eligibility
Key inclusion criteria
1. Newly diagnosed, histologically confirmed, locally advanced, stage III unresectable non small cell lung cancer (NSCLC).

Staging will be confirmed at screening by positron emission tomography-computed tomography (PET/CT) and brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast.
2. Eastern Cooperative Oncology Group (ECOG) performance status = 1.
3. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene translocation status available prior to randomization.
4. Provision of fresh or archival tumor tissue or discussion with Sponsor.
5. Adequate hematologic and end-organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior therapies including those targeting PD-1 or PD-L1 or chemotherapy, radiation, targeted therapy, biologic therapy, immunotherapy or investigational agent used to control non-small cell lung cancer (NSCLC).
2. History of severe hypersensitivity reactions to other monoclonal antibodies or any contraindication to the planned chemotherapy regimen.
3. History of, or ongoing, interstitial lung disease; pneumonitis requiring steroids; or clinically significant pericardial effusion.
4. Any active malignancy less than or equal to 2 years before randomization, with the exception of non-small cell lung cancer (NSCLC) and any locally recurring cancer that has been treated curatively.
5. Severe chronic or active infections including those requiring systemic antibacterial, antifungal or antiviral therapy; known human immunodeficiency virus (HIV) infection; untreated chronic hepatitis B or chronic hepatitis B virus carries or active hepatitis C; or active autoimmune disease.
6. Prior allogeneic stem cell transplantation or organ transplantation.
7. Significant cardiovascular disease or other condition which places the patient at risk.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/05/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/06/2019
Sample size
Target
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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California
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Kunming Shi
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Nanning
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Madrid
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Majadahonda, Madrid
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Malaga
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Oviedo
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Valencia
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Dalin
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Kaohsiung, San Ming Dist.
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Kaohsiung
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Niao-Sung Hsiang Kaohsiung County
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Taipei, Zhongzheng Dist.
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Birmingham
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Colchester
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London
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Maidstone
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Manchester
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Northwood
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Sheffield South Yorkshire
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
BeiGene
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed to compare the efficacy and safety of tislelizumab in combination with concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy versus cCRT alone, and tislelizumab given sequentially after cCRT versus cCRT alone, in newly diagnosed stage III subjects with locally advanced, unresectable non-small cell lung cancer (NSCLC). The primary endpoint is centrally-assessed progression free survival (PFS) in the intent-to-treat (ITT) population. .
Trial website
https://clinicaltrials.gov/study/NCT03745222
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marie Nguyen, MD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03745222