E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Untreated, PD-L1-Selected, and Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To compare progression-free survival (PFS) between Arm A (ociperlimab 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 (ociperlimab in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set |
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E.2.2 | Secondary objectives of the trial |
•To compare PFS between Arm A (ociperlimab 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 (ociperlimab 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 (ociperlimab in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) in the ITT Analysis Set •To further investigate the safety and tolerability of ociperlimab in combination with tislelizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 approximately 6 to 15 freshly cut unstained slides) or fresh biopsy (if archival tissue is not available) for central evaluation of PD-L1 levels and retrospective analysis of other biomarkers. 6.Tumors with PD-L1 expressed in ≥ 50% tumor cells as determined centrally (or locally in the US sites). 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 10^9/L −Platelets ≥ 75 x 10^9/L −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). Note: for France only: Serum creatinine ≤ 1.5 x ULN and estimated glomerular filtration rate or estimated creatinine clearance ≥ 60 mL/min/1.73 m2 by CKD-EPI and Cockcroft and Gault equations, respectively (Appendix 8). c.Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome). d.AST and ALT ≤ 2.5 x ULN or < 5 x ULN if hepatic metastases present. 10.Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 120 days after the last dose of study drug, and must have a negative urine or serum pregnancy test ≤ 7 days before randomization. 11.Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug. •A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility. •Males with known “low sperm counts” (consistent with “subfertility”) are not to be considered sterile for purposes of this study. |
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E.4 | Principal exclusion criteria |
1.Known mutation in a. EGFR gene b. ALK fusion oncogene c. BRAF V600E d. ROS1 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. Note: 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 ≤ 5 years before randomization except for the specific cancer under investigation in this study, those with a negligible risk of metastasis or death, and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, localized prostate cancer, or carcinoma in situ of the cervix or breast). 6.Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone [in Japan, prednisolone] or equivalent) or other immunosuppressive medication ≤ 14 days before randomization. 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. All patients 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, or patients who tested positive for COVID-19 antigen by a licensed test during screening. 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 human immunodeficiency virus (HIV) infection, or if HIV status is unknown, positive HIV test at Screening. 14.Any major surgical procedure ≤ 28 days before randomization. Patients must have recovered adequately from the toxicity and/or complications from the intervention before randomization. 15.Prior allogeneic stem cell transplantation or organ transplantation. 16.Any of the following cardiovascular risk factors: a.Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before randomization.b. Symptomatic pulmonary embolism diagnosed ≤ 28 days before randomization.c.Any history of acute myocardial infarction ≤ 6 months before randomization.d.Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (Appendix 6) ≤ 6 months before randomization.e.Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before randomization.f.Any history of cerebrovascular accident ≤ 6 months before randomization.g.Uncontrolled hypertension that cannot be managed by standard antihypertension medications ≤ 28 days before randomization.h.Any episode of syncope or seizure ≤ 28 days before randomization. 17.A history of severe hypersensitivity reactions to other monoclonal antibodies or a history of hypersensitivity to the ingredients of tislelizumab or ociperlimab. 18.Was administered a live vaccine ≤ 28 days before randomization. 19.Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that will be unfavorable for the administration of study drug, or affect the explanation of drug toxicity or AEs, or result in insufficient or impaired compliance with study conduct. 20.Women who are pregnant or are breastfeeding. 21. Concurrent participation in another therapeutic clinical study. |
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E.5 End points |
E.5.1 | 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 (ociperlimab 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 (ociperlimab in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• PFS as assessed by the BIRC in Arm A (ociperlimab 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 (ociperlimab 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 in Arm A (ociperlimab in combination with tislelizumab) and Arm B (pembrolizumab followed by placebo). PRO endpoints include the EORTC QLQC30’s global health status/QoL (GHS), physical function and fatigue scales, and the QLQ-LC13’s index score, dyspnea, coughing, hemoptysis and pain in chest, pain in arms/shoulders and peripheral neuropathy scales • TTD, defined as time from randomization to the first occurrence of 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 (ociperlimab in combination with tislelizumab) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 89 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Taiwan |
Australia |
China |
Georgia |
Japan |
Korea, Republic of |
Russian Federation |
Thailand |
Turkey |
United States |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as the timepoint when the final data point is collected from the last patient in the study. This is when the last patient dies, withdraws consent, completes all study assessments, or is lost to follow-up. Alternatively, the end of study is when the sponsor decides to terminate the study.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |