A Study of Ociperlimab With Tislelizumab Compared to Pembrolizumab in Participants With Untreated Lung Cancer

Study Overview
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Brief Summary
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The purpose of the study is to compare progression-free survival (PFS) between Arm A (ociperlimab in combination with tislelizumab) and Arm B (pembrolizumab in combination with placebo) as assessed by investigators according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and to compare overall survival (OS) between Arm A and Arm B.

Official Title
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A Phase 3, Randomized, Double-Blind Study of Ociperlimab, an Anti-TIGIT Antibody, in Combination With Tislelizumab Compared to Pembrolizumab in Patients With Previously Untreated, PD-L1-Selected, and Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer

Conditions
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NSCLC, Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Ociperlimab
* Drug: Pembrolizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically documented locally advanced or recurrent non-small cell lung cancer (NSCLC) that is not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic-nonsquamous or squamous NSCLC. No prior systemic treatment for metastatic NSCLC. Agreement to provide archival tissue or fresh biopsy (if archival tissue is not available). Tumors with PD-L1 expressed in ≥ 50% tumor cells. At least 1 measurable lesion as defined per RECIST v1.1. ECOG Performance Status ≤ 1. Key Exclusion Criteria: Known mutations in the epidermal growth factor receptor (EGFR) gene, anaplastic lymphoma kinase (ALK) fusion oncogene, BRAF V600E, or ROS1. Prior therapy with an anti-programmed cell death protein (anti-PD)-1, anti-PD-ligand (L)-1, anti-PD-ligand-2, anti-T-cell immunoglobulin and ITIM (anti-TIGIT) domain, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Tislelizumab plus Ociperlimab<br>Participants will receive tislelizumab 200 milligrams (mg) intravenously followed by ociperlimab 900 mg intravenously once every 3 weeks. | Drug: Tislelizumab<br>* Tislelizumab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A317;Drug: Ociperlimab<br>* Ociperlimab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A1217;|
| Active Comparator: Arm B: Pembrolizumab plus Placebo<br>Participants will receive pembrolizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks. | Drug: Pembrolizumab<br>* Pembrolizumab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: KEYTRUDA;Drug: Placebo<br>* Placebo infusions will consist of a sterile, normal saline solution.<br>|
| Placebo Comparator: Arm C: Tislelizumab plus Placebo<br>Participants will receive tislelizumab 200 mg intravenously followed by placebo intravenously once every 3 weeks. | Drug: Tislelizumab<br>* Tislelizumab is a monoclonal antibody formulated for intravenous injection.<br>* Other names: BGB-A317;Drug: Placebo<br>* Placebo infusions will consist of a sterile, normal saline solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) As Assessed By Investigators | PFS will be defined as the 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. | Up to approximately 40 months | 
| Overall Survival (OS) | OS will be defined as the time from the date of randomization to the date of death due to any cause. | Up to approximately 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS As Assessed By A Blinded Independent Review Committee | PFS will be defined as the 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. | Up to approximately 40 months | 
| Overall Response Rate (ORR) As Assessed By Investigators | ORR will be defined as the proportion of participants with a documented, confirmed complete response or partial response per RECIST v1.1. | Up to approximately 40 months | 
| Duration Of Response (DOR) As Assessed By Investigators | DOR will be defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of progression or death, whichever occurs first. | Up to approximately 40 months | 
| Health-related Quality Of Life (HRQoL): European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire Core 30 (EORTC QLQ-C30) | HRQoL will be assessed via patient-reported outcomes (PRO) using the EORTC QLQ-C30. The EORTC QLQ-C30 (Version 3) consists of Global health status/QoL (score range from 0=very poor to 7=excellent), 5 functioning scales (physical, role, emotional, cognitive, social), 8 symptom scales (fatigue, nausea/vomiting, pain, dyspnea, insomnia, constipation, diarrhea) and financial difficulties with scores ranging from 1 = Not at all to 4 = Very much. For the global health status/QoL and functioning scales, higher scores indicate better outcomes and for symptom scales, lower scores indicate better outcomes. | Within 7 days after permanent treatment discontinuation | 
| HRQoL: EORTC Lung Cancer Module Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) HRQoL will be assessed via PRO using the EORTC QLQ-LC13. | QLQ-LC13 consists of 10 scales, scores ranging from 1 = not at all to 4 = very much, and 2 questions regarding use of pain medication (yes/no) and if yes, did it help (1 = not at all to 4 = very much). In symptom scales, lower scores indicate better outcomes. | Within 7 days after permanent treatment discontinuation | 
| HRQoL: European Quality of Life-5 Level- 5 Dimension (EQ-5D-5L) Questionnaire | HRQoL will be assessed via PRO using the EQ-5D-5L. The EQ-5D-5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and a visual analog scale (VAS). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The VAS records the respondent's self-rated health on a 0 to 100 scale, with 100 = the best health you can imagine and 0 = 'the worst health you can imagine. Lower scores in descriptive dimension indicate better HRQoL and higher VAS scores indicates better health state. | Within 7 days after permanent treatment discontinuation | 
| Time To Deterioration (TTD) | TTD will be analyzed using PRO scores, and will be defined as worsening scores of ≥10 points from baseline for 2 consecutive assessments or 1 assessment followed by death from any cause. | Within 7 days after permanent treatment discontinuation | 
| Number Of Participants Experiencing Adverse Events (AEs) | The incidence and severity of AEs will be determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0). | 90 days (±14) after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced, Unresectable, Metastatic, Tislelizumab, BGB-A317, Ociperlimab, BGB-A1217, Pembrolizumab, Anti-TIGIT