Previously treated Non-Small Cell Lung Cancer in the second or third line setting. 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
Interventions
JHL2108
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Trade Name: Docetaxel AqVida 20 mg/ml konzentrat zur Herstellung einer Infusionslösung
Pr
Sponsors
BeiGene Ltd., c/o BeiGene USA Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent and can understand and 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 confirmed disease which is currently locally advanced or metastatic NSCLC of either squamous or non-squamous histology. 4. With disease progression during or following treatment with at least one platinum-containing regimen. • Patients who received prior neo-adjuvant or adjuvant chemotherapy but progressed within 6 months after last dose are eligible provided the target lesion(s) have not been previously treated with local therapy (radiation) or the target lesion(s) within the field of local therapy have subsequently progressed as defined per RECIST v1.1 • Anti-EGFR treatment with disease progression as the treatment outcome is counted as a line of therapy. • Anticancer agents used for pleurodesis are not counted as a line of therapy. 5. Patients must be able to provide archival/fresh tumor tissues (FFPE blocks or approximately 11 [at least 5] freshly cut unstained FFPE slides) for biomarker analysis to assess PD-L1 expression and, provided sufficient tissue, including tumor mutational burden (TMB), and gene expression profiling (GEP). Documentation of wild type status of EGFR by tissue-based test must be provided for patients with non-squamous NSCLC prior to enrollment. For undocumented cases, archival/fresh tumor tissues (FFPE blocks or 6 freshly cut unstained FFPE slides) are required for central assessment of EGFR mutation. In the absence of archival tumor tissues, a fresh biopsy of a tumor lesion at baseline (within 42 days before Cycle 1 Day 1) is mandatory (written informed consent is required prior to fresh tumor biopsies). 6. ECOG PS =1. 7. Adequate hematologic and end-organ function, as defined by the following laboratory results (obtained =28 days prior to randomization): • Absolute neutrophil count (ANC) = 1.5 × 109/L, platelets = 100 × 109/L, and hemoglobin = 90 g/L. Note: Patients must not have required a blood transfusion or growth factor support within the 14 days before sample collection • Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 6) • Total serum bilirubin =1.5 × upper limit of normal (ULN) - =3 × ULN, if Gilbert's syndrome or if indirect bilirubin concentrations are suggestive of extrahepatic source of the elevation • Aspartate and alanine aminotransferase (AST and ALT) =3 × ULN - =5 × ULN, if liver metastases 8. Females of childbearing potential must be willing to practice highly effective method of birth control (Appendix 4) for the duration of the study, and, for patients in Arm A, for at least 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test within 7 days of randomization. 9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and, for patients in Arm A, for at least 120 days after the last dose of tislelizumab. 10. Expected life span > 12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 615 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for th
Exclusion criteria
Exclusion criteria: 1. Received prior docetaxel treatment for metastatic disease or prior immune checkpoint inhibitor therapies targeting PD-1, PD-L1 or CTLA-4. 2. Diagnosed with NSCLC that harbors EGFR sensitizing or driver mutation or ALK gene translocation. 3. Patients with toxicities (as a result of prior anticancer therapy including radiation) which have not recovered to baseline or stabilized, except for AEs not constituting a likely safety risk (including but not limited to alopecia, rash, pigmentation, specific laboratory abnormalities etc). 4. Received chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin), or investigational agent, used to control cancer = 28 days (or = 5 half lives, whichever is shorter) prior to randomization 5. Received any herbal medicine used to control cancer within 14 days prior to randomization. 6. History of severe hypersensitivity reactions to other mAbs. 7. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc. 8. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline. 9. Clinically significant pericardial effusion. 10. Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to randomization. 11. Active Leptomeningeal disease or uncontrolled, untreated brain metastasis as per protocol 12. Major surgical procedure requiring general anesthesia, or significant traumatic injury = 28 days prior to randomization, or anticipation of need for major surgical procedure during the course of the study. •Placement of vascular access device is not considered major surgery. 13. Malignancy other than NSCLC 14. Severe chronic or active infections (including tuberculosis infection) requiring systemic antibacterial, antifungal, antiviral therapy, or systemic oral/IV antibiotics within 14 days prior to randomization. • Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. 15. A known history of human immunodeficiency virus (HIV) infection. 16. Patients with active/symptomatic carrier or chronic hepatitis B virus (HBV) whose HBV DNA = 500 IU/mL (or = 2500 copies/mL) should be excluded. 17. Active autoimmune diseases or history of autoimmune diseases that may relapse should be excluded. 18. Requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of randomization. 19. With 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. 20. Any of the following cardiovascular criteria: • Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, = 28 days before randomization. • Symptomatic pulmonary embolism = 28 days before randomization. • Acute myocardial infarction = 6 months prior to randomization. • Heart failure of New York Heart Association Classification III or IV (see Appendix 5) =6 months prior to randomization • Grade =2 ventricular arrhythmia =6 months prior to randomization • Cerebral vascular accident or transient ischemic attack = 6 months pr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy, as measured by overall survival (OS), of tislelizumab with docetaxel in the second- or third-line setting in patients with non-small cell lung cancer (NSCLC) who have progressed on a prior platinum-containing regimen. A comparison of the treatment arms will be performed in: o The intent-to-treat (ITT) analysis set o The program cell death protein ligand-1 (PD-L1) positive analysis set, where PD-L1 positive is defined as =25% of tumor cells (TCs) with PD-L1 membrane staining via the Ventana SP263 assay;Secondary Objective: 1. To compare the efficacy of tislelizumab and docetaxel as measured by objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in: o The ITT analysis set o The PD-L1 positive analysis set 2. To compare health-related quality of life (HRQoL) between tislelizumab and docetaxel 3. To evaluate the safety and tolerability of tislelizumab versus docetaxel;Primary end point(s): OS - defined as the time from the date of randomization to the date of death due to any cause in the ITT and PD-L1 positive analysis set.;Timepoint(s) of evaluation of this end point: as per protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR – defined as the proportion of patients in the ITT and PD-L1 positive analysis set who had a CR or PR as assessed by the investigator per RECIST v1.1 • DoR – defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the investigator per RECIST v1.1, or death from any cause, whichever comes first, in the ITT and PD-L1 positive analysis set • PFS – defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurs first, in the ITT and PD-L1 positive analysis set • HRQoL – measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) and Core 30 (EORTC QLQ-C30), and European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) scale • Incidence and severity of TEAEs graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.03;Timepoint(s) of evaluation of this end point: As per protocol | — |
Countries
Brazil, Bulgaria, China, Lithuania, Mexico, New Zealand, Poland, Russian Federation, Slovakia, Turkey
Contacts
Public ContactBeiGene Clinical support
BeiGene Ltd., c/o BeiGene USA Inc.
Outcome results
None listed