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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

NCT03745222

Description:

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. .

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT03745222

Trial Eligibility

Document

Title

  • Brief 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317-NSCL-001
  • SECONDARY ID: U1111-1216-4294
  • SECONDARY ID: 2018-001132-22
  • NCT ID: NCT03745222

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
TislelizumabBGB-A317Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy
Concurrent chemoradiotherapy (cCRT)Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy

Purpose

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 Arms

NameTypeDescriptionInterventions
Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapyExperimentalTislelizumab 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
  • Tislelizumab
  • Concurrent chemoradiotherapy (cCRT)
Arm 2: Placebo + cCRT followed by tislelizumab monotherapyExperimentalPlacebo 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.
  • Tislelizumab
  • Concurrent chemoradiotherapy (cCRT)
Arm 3: Placebo + cCRT followed by placebo monotherapyPlacebo ComparatorPlacebo 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.
  • Concurrent chemoradiotherapy (cCRT)

Eligibility 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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Overall Survival (OS)
Time Frame:Up to approximately 5 years; date of randomization to date of death from any cause.
Safety Issue:
Description:Overall survival was defined as the time between randomization of treatment and death from any cause.
Measure:Overall Survival at 24 Months
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Overall survival was defined as the time between randomization of treatment and death from any cause.
Measure:Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response
Time Frame:Up to approximately 5 years
Safety Issue:
Description: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).
Measure:Duration of Response
Time Frame:Up to approximately 5 years
Safety Issue:
Description: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.
Measure:Percentage of Participants Alive and Progression-Free at 12 Months (APF12)
Time Frame:Up to 12 months
Safety Issue:
Description: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
Measure:Percentage of Participants Alive and Progression-free at 18 Months (APF18)
Time Frame:Up to approximately 18 months
Safety Issue:
Description: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
Measure:Time to Distant Metastasis (TTDM)
Time Frame:Up to approximately 5 years
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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."
Measure: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
Safety Issue:
Description: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.
Measure:Percentage of Participants Who Would Have Continued on to Monotherapy Phase
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Included the percentage of participants who would have received at least one dose of tislelizumab or placebo in the monotherapy phase before progression.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Celgene

Trial Keywords

  • Locally Advanced, Unresectable Non-Small Cell Lung Cancer
  • Non-Small Cell Lung Cancer
  • NSCLC
  • Randomized
  • BGB-A317
  • Tislelizumab
  • PD-1

Last Updated

July 15, 2020