Previously Untreated, PD-L1-Selected, and Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
BeiGene, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments. 2.Age = 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place). 3.Histologically or cytologically documented locally advanced or recurrent NSCLC that is not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic nonsquamous or squamous NSCLC. 4.No prior systemic treatment for metastatic NSCLC. 5.Agreement to provide archival tissue (formalin-fixed paraffin-embedded block containing tumor [preferred] or 6 to 15 freshly cut unstained slides) or fresh biopsy (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers. 6.Tumors with PD-L1 TC = 50% expression as centrally determined. 7.At least 1 measurable lesion as defined per RECIST v1.1. 8.ECOG Performance Status = 1. 9.Adequate organ function as indicated by the following laboratory values during screening: a.Patients must not have required blood transfusion or growth factor support = 14 days before sample collection at screening for the following: -Absolute neutrophil count (ANC) = 1.5 x 109/L -Platelets = 75 x 109/L or 100 x 109/L in chemotherapy combination studies -Hemoglobin = 90 g/L b.Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated Glomerular Filtration Rate = 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 8). c.Serum total bilirubin = 1.5 x ULN (total bilirubin must be =65 years) yes F.1.3.1 Number of subjects for this age range 155
Exclusion criteria
Exclusion criteria: 1.Known sensitizing mutation in the EGFR gene or an ALK fusion oncogene. Note: Patients with nonsquamous NSCLC whose EGFR mutational status is unknown will be required to have a tissue-based EGFR test either locally or centrally at prescreening. Patients found to have EGFR-sensitizing mutations will be excluded. 2.Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. 3.Active leptomeningeal disease or uncontrolled, untreated brain metastasis. •Patients with a history of treated and, at the time of screening, stable central nervous system (CNS) metastases are eligible, provided they meet all the following: -Brain imaging at screening shows no evidence of interim progression, patient is clinically stable for at least 2 weeks and without evidence of new brain metastases. -Measurable and/or evaluable disease outside the CNS. -No ongoing requirement for corticosteroids as therapy for CNS disease; off steroids 3 days before randomization; anticonvulsants at a stable dose are allowed. -No stereotactic radiation or whole-brain radiation within 14 days before randomization. 4.Active autoimmune diseases or history of autoimmune diseases that may relapse. 5.Any active malignancy = 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast). 6.Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication = 14 days before randomization. b.Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption.c.Short course (= 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen. 7.Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or = Grade 3 hypoalbuminemia = 14 days before randomization. 8.Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks of intervention). Patients with symptomatic pleural effusion are excluded unless the patient undergoes a therapeutic thoracentesis or has had pleurodesis (more than 2 weeks prior) and has subsequently stable effusions. 9.History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening 10.Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before randomization. 11.Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA > 500 IU/mL (or>2500 copies/mL) at screening. 12.Patients with active hepatitis C. 13.Known history of HIV infection. 14.Any major surgical procedure = 28 days before randomization. Patients must have recovered adequately from the toxicity and/or complications from the int
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare progression-free survival (PFS) between Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the Intent-to-Treat (ITT) Analysis Set as assessed by investigators according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) • To compare overall survival (OS) between Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set;Secondary Objective: •To compare PFS between Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set as assessed by the Blinded Independent Review Committee (BIRC) according to RECIST v1.1 •To compare the overall response rate (ORR) and duration of response (DOR) between Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set as assessed by investigators according to RECIST v1.1 •To compare health-related quality of life (HRQoL) and time to deterioration (TTD) between Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set •To further investigate the safety and tolerability of BGB-A1217 in combination with tislelizumab;Primary end point(s): • PFS as assessed by investigators (time from the date of randomization to the date of the first objectively documented tumor progression per RECIST v1.1, or death, whichever occurs first) in the ITT Analysis Set of Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) • OS (time from the date of randomization to the date of death due to any cause) in the ITT Analysis Set of Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS as assessed by the BIRC in Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) • ORR as assessed by investigators (proportion of patients with a documented, confirmed complete response [CR] or partial response [PR] per RECIST v1.1) and DOR as assessed by investigators (time from the first determination of an objective response per RECIST v1.1 until the first documentation of progression or death, whichever occurs first) in Arm A (BGB-A1217 in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) • HRQoL as assessed via patient-reported outcomes (PRO) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), its lung cancer module Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13), and the 5-Level EuroQol 5-Dimension (EQ-5D-5L) questionnaire • TTD, defined as worsening scores (10-point change, to be defined in the Statistical Analysis Plan [SAP] if otherwise) for 2 consecutive assessments or 1 assessment followed by death from any cause before the next scheduled data collection • The incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) in Arm A (BGB-A1217 in combination with tislelizumab) | — |
Countries
Australia, China, France, Georgia, Germany, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United States
Contacts
Public ContactBeiGene Clinical Support
BeiGene, Inc.
Outcome results
None listed