Clinical Trials /

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 PFS in the intent-to-treat (ITT) population. Newly diagnosed stage III subjects with histologically confirmed, locally advanced, unresectable NSCLC are eligible.

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

Terminated

Phase:

Phase 3

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 PFS in the intent-to-treat (ITT) population. Newly diagnosed stage III subjects with histologically confirmed, locally advanced, unresectable NSCLC are eligible.

Trial Arms

NameTypeDescriptionInterventions
Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapyExperimentalTislelizumab is given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 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 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 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. EGFR mutation and 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 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:Randomization to date of objective disease progression or death, assessed up to approximately 5 years
Safety Issue:
Description:The time from the date of randomization to the date of the first objectively documented tumor progression as assessed by blinded independent central review per RECIST v1.1 or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Randomization to death due to any cause, assessed up to approximately 5 years
Safety Issue:
Description:Randomization to death due to any cause
Measure:Overall survival (OS) at 24 months
Time Frame:Randomization to 24 months
Safety Issue:
Description:The proportion of subjects alive at 24 months after randomization.
Measure:Objective response rate (ORR)
Time Frame:Randomization to date of objective disease progression or death, assessed up to approximately 5 years
Safety Issue:
Description:The proportion of subjects in the ITT population who had complete response (CR) or partial response (PR) as assessed by blinded independent central review per RECIST v1.1.
Measure:Duration of response (DoR)
Time Frame:First documented objective response (RECIST 1.1) until date of objective disease progression or death, assessed up to approximately 5 years
Safety Issue:
Description: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:Proportion of subjects alive and progression-free at 12 months (APF12)
Time Frame:Up to approximately 12 months
Safety Issue:
Description:The proportion of subjects progression free at 12 months (APF12) will be summarized using the Kaplan-Meier estimate of PFS at 12 months.
Measure:Proportion of subjects alive and progression-free at 18 months (APF18)
Time Frame:Up to approximately 18 months
Safety Issue:
Description:The proportion of subjects alive and progression free at 18 months (APF18) will be summarized by using the Kaplan-Meier curve.
Measure:Time to distant metastasis (TTDM)
Time Frame:Randomization until first date of distant metastasis or death, assessed up to approximately 5 years
Safety Issue:
Description:Is defined as the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field according to RECIST v1.1 or proven by biopsy.
Measure:Adverse Events (AEs)
Time Frame:From enrollment until 90 days after the last dose of study treatment
Safety Issue:
Description:Safety and tolerability will be assessed from adverse events (using NCI CTCAE v5.0), laboratory tests, vital signs, ECOG performance status, physical exams, concomitant medications, and dose modifications.
Measure:European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Is a 30-item, psychometrically robust, cross- culturally accepted and internationally validated questionnaire designed to be applicable to a broad spectrum of cancer subjects as a core questionnaire, assessing QoL, psychosocial burden and physical symptoms.
Measure:European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire lung cancer module (EORTC QLQ-LC13)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Subjects' disease-related symptoms will be assessed using the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13; referred to here as the LC13) which is a lung cancer specific PRO and the first module to be used in conjunction with the EORTC QLQ-C30.
Measure:Proportion of subjects who continue to monotherapy phase
Time Frame:Randomization to the first dose in the monotherapy phase (Approximately Study Day 43)
Safety Issue:
Description:Proportion of subjects who receive at least one dose of tislelizumab or placebo in the monotherapy phase before progression as determined by blinded independent central review per RECIST v1.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
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