A Study to Compare Ociperlimab Plus Tislelizumab Versus Durvalumab Following Concurrent Chemoradiotherapy (cCRT) in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to compare progression-free survival (PFS) between Arm A (ociperlimab in combination with tislelizumab) and Arm C (Durvalumab) as assessed by the Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in participants with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.

Official Title
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A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in Patients With Locally Advanced, Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer Whose Disease Has Not Progressed After Concurrent Chemoradiotherapy

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Durvalumab
* Drug: Ociperlimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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). Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III NSCLC (AJCC Cancer Staging Manual 2017, derived from IASLC) prior to initiation of cCRT. Participant must have completed at least 2 cycles of platinum-based chemotherapy concurrent with radiotherapy Participants must have not experienced PD following definitive, platinum-based cCRT. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1. Participants must have adequate organ function Agree to provide archival tissue (formalin-fixed paraffin-embedded block containing tumor [preferred] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy obtained prior to cCRT (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers. Key Exclusion Criteria: Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody or drugs specifically targeting T-cell co-stimulation or checkpoint pathways. Diagnosed with NSCLC that harbors an epidermal growth factor receptor (EGFR) sensitizing mutation, anaplastic lymphoma kinase (ALK) gene translocation, ROS1 gene translocation or RET gene rearrangement. Participants who received systemic anticancer treatment besides the specified cCRT. Any unresolved toxicity CTCAE > Grade 2 from the prior cCRT. Active autoimmune diseases or history of autoimmune diseases that may relapse. 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 the first dose of study treatment. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before the first dose of study treatment. Note: Antiviral therapy is permitted for participants with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. NOTE: Other protocol 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: ociperlimab + tislelizumab<br>ociperlimab combined with tislelizumab every 3 weeks | Drug: Tislelizumab<br>* administered by intravenous infusion<br>* Other names: BGB-A317;Drug: Ociperlimab<br>* administered by intravenous infusion<br>* Other names: BGB-A1217;|
| Experimental: Arm B: tislelizumab<br>tislelizumab every 3 weeks | Drug: Tislelizumab<br>* administered by intravenous infusion<br>* Other names: BGB-A317;|
| Experimental: Arm C: durvalumab<br>durvalumab every 2 weeks or 4 weeks | Drug: Durvalumab<br>* administered by intravenous infusion<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 the Independent Review Committee (IRC) | Time from the date of randomization to the date of first documentation of disease progression assessed by the IRC per RECIST v1.1 or death, whichever occurs first | Up to 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | defined as the time from the date of randomization until the date of death due to any cause | Up to 16 months | 
| Overall Response Rate (ORR) | defined as the proportion of participant who achieve a complete response (CR) or partial response (PR) assessed by both the IRC and investigators per RECIST v1.1 | Up to 16 months | 
| Duration of Response (DOR) | defined as the time from the first determination of a confirmed objective response assessed by both the IRC and investigators per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first | Up to 16 months | 
| Time to death or distant metastasis (TTDM) as assessed by the investigator | defined as the time from the date of randomization until the first date of distant metastasis assessed by both the IRC and investigators, or death. Distant metastasis is defined as any new lesion that is outside of the radiation field per RECIST v1.1 or proven by biopsy. | Up to 16 months | 
| Progression-Free Survival 2 (PFS2) | defined as the time from randomization to the disease progression after next line of treatment, or death from any cause, whichever occurs first | Up to 16 months | 
| 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). | Up to 16 months | 
| Health Related Quality of Life (HRQoL) as assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) | The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 (Not at all), 2 (A little), 3 (Quite a bit) and 4 (Very much). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 (very poor) to 7 (excellent). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome. | Up to 16 months | 
| Health Related Quality of Life (HRQoL)as assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) A score of 1-4 will be administrated for each item in QLQ-LC13. The higher scores will indicate the worse outcomes. | Up to 16 months | 
| Health Related Quality of Life (HRQoL) as assessed by European Quality of Life-5 Dimensions (EQ-5D-5L) | EQ-5D-5L - Is the EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the participant's health state. | Up to 16 months | 
| Serum concentration of ociperlimab |  | Up to 30 minutes postdose | 
| Serum concentration of tislelizumab |  | Up to 30 minutes postdose | 
| Immunogenic responses to BGB-A1217 as assessed by the detection of anti-drug antibodies (ADAs) |  | Up to 16 months | 
| Immunogenic responses to Tislelizumab as assessed by the detection of anti-drug antibodies (ADAs) |  | Up to 16 months | 
| Evaluate PD-L1 and TIGIT expression in archival and/or fresh tumor tissues | before study treatment or at disease progression/reoccurrence, and their association with clinical efficacy. | Up to 16 months |