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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 (RATIONALE001)

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ClinicalTrials.gov Identifier: NCT03745222
Recruitment Status : Terminated (BeiGene and Celgene Corporation terminated the parties' global collaboration for the compound, pending the acquisition of Celgene by Bristol Myers Squibb)
First Posted : November 19, 2018
Results First Posted : July 15, 2020
Last Update Posted : July 15, 2020
Sponsor:
Collaborator:
BeiGene
Information provided by (Responsible Party):
Celgene

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. .

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Tislelizumab Drug: Concurrent chemoradiotherapy (cCRT) Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : May 22, 2019
Actual Primary Completion Date : June 26, 2019
Actual Study Completion Date : June 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)
Other Name: BGB-A317

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

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.
Drug: Tislelizumab
PD-1 inhibitor (monoclonal antibody against PD-1)
Other Name: BGB-A317

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

Other: Placebo
Placebo

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

Other: Placebo
Placebo




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019 ]
    Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first. Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 5 years; date of randomization to date of death from any cause. ]
    Overall survival was defined as the time between randomization of treatment and death from any cause.

  2. Overall Survival at 24 Months [ Time Frame: Up to approximately 24 months ]
    Overall survival was defined as the time between randomization of treatment and death from any cause.

  3. Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response [ Time Frame: Up to approximately 5 years ]
    Overall Response was defined as percentage of participants who had a radiologic confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines, between Day 1 of treatment and subsequent anti-cancer therapy, death or study discontinuation. Complete response was defined as the disappearance of all target lesions; partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease (PD).

  4. Duration of Response [ Time Frame: Up to approximately 5 years ]
    Duration of Response is defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by blinded independent central review per RECIST v1.1, or death from any cause, whichever comes first.

  5. Percentage of Participants Alive and Progression-Free at 12 Months (APF12) [ Time Frame: Up to 12 months ]
    Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first

  6. Percentage of Participants Alive and Progression-free at 18 Months (APF18) [ Time Frame: Up to approximately 18 months ]
    Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first

  7. Time to Distant Metastasis (TTDM) [ Time Frame: Up to approximately 5 years ]
    TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that is outside of the radiation field according to RECIST v1.1 or proven by biopsy.

  8. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. ]
    TEAEs include any adverse events (AEs) that had an onset date or a worsening in severity from baseline on or after the first dose of study drug up to 30 days following study drug discontinuation or initiation of new anticancer therapy, whichever occurred first. TEAEs also included all immune-related AEs recorded up to 90 days after the last dose of tislelizumab or placebo, regardless of whether or not the particpant started a new anticancer therapy. In addition, any serious AE with an onset date more than 30 days after the last dose of study drug that is assessed by the investigator as related to study drug were considered a TEAE."

  9. 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 [ Time Frame: Up to approximately 5 years ]
    The EORTC QLQ-C30 is a 30-item, questionnaire assessing quality of life (QoL), psychosocial burden and physical symptoms. It is classified into 15 domains: 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); each item is measured on a 4 point response scale; (not at all, a little, quite a bit, very much), with the exception of the 2 items measuring global health and QoL, (measured on a 7-point response scale). Scores are linearly transformed to 0 to 100 scores. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions; higher scores = better QoL, better functioning, or more severe symptoms, respectively. The LC13 covers 13 typical symptoms of lung cancer patients, such as coughing, pain, dyspnea, sore mouth, peripheral neuropathy, and hair loss.

  10. Percentage of Participants Who Would Have Continued on to Monotherapy Phase [ Time Frame: Up to approximately 5 years ]
    Included the percentage of participants who would have received at least one dose of tislelizumab or placebo in the monotherapy phase before progression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745222


Locations
Show Show 164 study locations
Sponsors and Collaborators
Celgene
BeiGene
Investigators
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Study Director: Marie Nguyen, MD Celgene
  Study Documents (Full-Text)

Documents provided by Celgene:
Study Protocol  [PDF] September 20, 2018
Statistical Analysis Plan  [PDF] May 7, 2019

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03745222    
Other Study ID Numbers: BGB-A317-NSCL-001
U1111-1216-4294 ( Other Identifier: WHO )
2018-001132-22 ( EudraCT Number )
First Posted: November 19, 2018    Key Record Dates
Results First Posted: July 15, 2020
Last Update Posted: July 15, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer
NSCLC
Randomized
BGB-A317
Tislelizumab
PD-1
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms