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OpenTrials
Completed

NCT Number: NCT03358875

Comparison of Efficacy and Safety of Tislelizumab (BGB-A317) Versus Docetaxel as Treatment in the Second- or Third-line Setting in Participants With Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to show that tislelizumab will improve overall survival in participants with Stage IIIB or IV non-small cell lung cancer when compared to docetaxel in second or third-line treatment setting.

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital de Amor Barretos, Barretos, Brazil

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About this study

This is a randomized, open-label, multicenter Phase 3 study in adult participants with histologically confirmed, locally advanced or metastatic (Stage IIIB or IV), NSCLC (squamous or non-squamous) who have disease progression during or after a platinum-containing regimen.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Age ≥ 18 years.
  • Signed Informed Consent Form.
  • Histologically confirmed locally advanced or metastatic (Stage IIIB or IV) NSCLC of either squamous or non-squamous histology types with disease progression during or following treatment with at least one platinum-containing regimen, but no more than 2 lines of systemic therapy.
  • Participants must be able to provide fresh or archival tumor tissues for central assessment of PD-L1 expression in tumor cells. Participants with non-squamous histology must provide evidence of not harboring sensitizing epidermal growth factor (EGFR) mutation tested by a histology-based method.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Adequate hematologic and end-organ function.
  • Expected life span > 12 weeks.
  • Willing to be compliance with birth control requirement during pre-specified study participating period

Key Exclusion Criteria:

  • Prior therapies of docetaxel or treatment targeting programmed cell death protein 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte associated protein 4 (CTLA-4).
  • Harboring EGFR sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
  • Unresolved side effects of Grade 2 and above from prior anti-cancer therapies, except for adverse events (AEs) not constituting a likely safety risk (e.g. alopecia, rash, pigmentation, specific lab abnormalities).
  • History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
  • History of interstitial lung disease, non-infectious pneumonitis or participants with significantly impaired pulmonary function, or who require supplemental oxygen at baseline.
  • With uncontrollable pleural effusion, pericardial effusion, or clinically significant ascites requiring interventional treatment.
  • Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
  • Severe chronic or active infection requiring systemic treatment.
  • Known human immunodeficiency virus (HIV) infection, participants with untreated chronic hepatitis B, active vaccination treatment.
  • Insufficient cardiac functions and other underlying unfavorable cardiovascular conditions.
  • Prior allogeneic stem cell transplantation or organ transplantation.
  • Active autoimmune diseases or history of autoimmune diseases that may relapse.
  • With conditions requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.
  • With severe underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse that may affect the explanation of drug toxicity or AEs or result in impaired compliance with study conduct.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Tislelizumab

Drug

Tislelizumab administered by intravenous (IV) infusion

Other names: BGB-A317, TEVIMBRA®

docetaxel

Drug

Docetaxel administered as an IV infusion over 1 hour

Primary outcomes

  1. Overall Survival (OS) in All Participants (Co-primary Endpoint)

    Time frame: From randomization to the data cutoff date of 10 August 2020; up to 32.4 months

    OS was defined as the time from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Data for participants who did not have postbaseline information were censored at the date of randomization.

  2. Overall Survival (OS) in Programmed Cell Death Protein Ligand-1 (PD-L1)-Positive Participants (Co-primary Endpoint)

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    OS was defined as the time from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Data for participants who did not have postbaseline information were censored at the date of randomization.

Secondary outcomes

  1. Objective Response Rate (ORR) in All Participants

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    Objective response rate is defined as the percentage of participants who had a complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the chest, abdomen, and pelvis.

    CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

    PR: At least a 30% decrease in the size of target lesions and no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions.

  2. Objective Response Rate in PD-L1-Positive Participants

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    Objective response rate is defined as the percentage of participants who had a complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the chest, abdomen, and pelvis.

    CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

    PR: At least a 30% decrease in the size of target lesions and no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions.

  3. Duration of Response (DOR) for All Responders

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    DoR was defined as the time from the first documented objective response to documented disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.

    Median DOR was estimated using the Kaplan-Meier method.

    Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.

  4. Duration of Response (DOR) in PD-L1-Positive Responders

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    DoR was defined as the time from the first documented objective response to documented disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.

    Median DOR was estimated using the Kaplan-Meier method.

    Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.

  5. Progression-free Survival (PFS) in All Participants

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first.

    Median PFS was estimated using the Kaplan-Meier method.

  6. Progression-free Survival in PD-L1 Positive Participants

    Time frame: From randomization up to the final efficacy analysis data cut-off date of 15 July 2021; Up to 43 months

    PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first.

    Median PFS was estimated using the Kaplan-Meier method.

  7. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score

    Time frame: Baseline and Cycle 6 (each cycle was 3 weeks)

    The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and two global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS/QoL score indicates better quality of life.

  8. Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 Items (QLQ-LC13) Coughing, Dyspnoea, and Chest Pain Scores

    Time frame: Baseline and Cycle 6 (each cycle was 3 weeks)

    The EORTC QLQ-LC13 is the lung cancer module of the QLQ-C30 and measures lung cancer-specific disease and treatment symptoms. It includes 13 questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. Lower scores indicate an improvement in symptoms.

  9. Change From Baseline in European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS)

    Time frame: Baseline and Cycle 6 (each cycle was 3 weeks)

    The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.

  10. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: From first dose of study drug to 30 days after last dose, up to the study completion date cut-off date of 18 January 2024 (up to approximately 63 months)

    An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.

    The investigator assessed the severity of each AE and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 as defined below:

    • Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
    • Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living.
    • Grade 3: Severe or medically significant but not immediately life threatening. hospitalization or prolongation of hospitalization indicated; disabling; limiting selfcare activities of daily living.
    • Grade 4: Life threatening consequences; urgent intervention indicated.
    • Grade 5: Death related to AE.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

A Phase 3, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of BGB-A317 (Anti-PD1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer Who Have Progressed on a Prior Platinum-Containing Regimen

Acronym: RATIONALE-303

Important dates

Study start
2017
Primary completion
2021
Study completion
2024
First posted
Dec 2, 2017
Registry last updated
Feb 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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