A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without chemotherapy. This study is structured as a master protocol with separate sub- studies. Sub-study 1 includes participants with non-small cell lung cancer (NSCLC) with high programmed cell death protein ligand-1 (PD-L1) expression (≥ 50%), and Sub-study 2 includes participants with NSCLC with low or negative (PD-L1) expression (< 50%).

Official Title
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Master Protocol: A Phase 2, Open-label, Multi-arm Study of Tislelizumab in Combination With Investigational Agents With or Without Chemotherapy in Patients With Previously Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer

Conditions
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Metastatic Non-small Cell Lung Cancer, Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: BGB-A445
* Drug: LBL-007
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: pemetrexed
* Drug: Paclitaxel
* Drug: Nab paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed NSCLC (nonsquamous or squamous) that is locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC. No prior systemic treatment given as primary therapy for metastatic NSCLC. Prior adjuvant/neoadjuvant chemotherapy or definitive chemoradiation/adjuvant radiotherapy for locally advanced disease is allowed provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months before randomization/enrollment. Evaluable tumor PD-L1 expression as determined by a local laboratory or by central laboratory on archival tumor tissue or fresh biopsy. Patients with unknown PD-L1 expression will not be eligible for this study. At least 1 measurable lesion as defined per RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Exclusion Criteria: Has mixed small cell lung cancer. Participants with known actionable mutations for which a targeted therapy has been approved by the local health authority will be excluded. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, anti-LAG-3 or any other antibody or drug targeting T-cell costimulation or immune checkpoint pathways. Note: Patients who received prior neoadjuvant, adjuvant or immuno-oncology therapies targeting PD-1 or PD-L1 in consolidation are eligible, if there has been a treatment-free interval of ≥ 6 months from last dose of immuno-oncology therapy prior to radiologic recurrence of disease. Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before randomization/enrollment. Active leptomeningeal disease or uncontrolled, untreated brain metastasis, or active autoimmune diseases. NOTE: Other protocol and sub-study protocol defined 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: Sub-study 1: Experimental Arm 1A<br>Tislelizumab + BGB-A445 | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>Drug: BGB-A445<br>* Administered by intravenous infusion<br>|
| Experimental: Sub-study 1: Experimental Arm 2A<br>Tislelizumab + LBL-007 | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>Drug: LBL-007<br>* Administered by intravenous infusion<br>|
| Experimental: Sub-study 1: Reference Arm<br>Tislelizumab alone | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>|
| Experimental: Sub-study 2 : Experimental Arm 1A<br>Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445 | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>Drug: BGB-A445<br>* Administered by intravenous infusion<br>Drug: LBL-007<br>* Administered by intravenous infusion<br>Drug: Carboplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Cisplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: pemetrexed<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Nab paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>|
| Experimental: Sub-study 2: Experimental Arm 1B<br>Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007 | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>Drug: LBL-007<br>* Administered by intravenous infusion<br>Drug: Carboplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Cisplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: pemetrexed<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Nab paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>|
| Active Comparator: Sub-study 2: Reference Arm<br>Tislelizumab + investigator's choice of histology-appropriate chemotherapy | Drug: Tislelizumab<br>* Administered by intravenous infusion<br>Drug: Carboplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Cisplatin<br>* Investigator's choice; administered by intravenous infusion<br>Drug: pemetrexed<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>Drug: Nab paclitaxel<br>* Investigator's choice; administered by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed overall response rate (ORR) | ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 | Up to 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS is defined as the time from date of randomization, or the first dose for safety lead-in participants , until first documentation of progression or death, whichever comes first, as assessed by the investigator using RECIST v1. | Up to 3 Years | 
| Duration of Response (DOR) | DOR is defined as the time from the first determination of a confirmed response per RECIST v1.1 until the first documentation of progression or death, whichever comes first as assessed by the investigator | Up to 3 Years | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with a best overall response of a complete response, partial response, or durable stable disease, as assessed by the investigator using RECIST v1.1 | Up to 3 Years | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants with a best overall response of complete response, partial response, or stable disease, as assessed by the investigator using RECIST v1.1 | Up to 3 Years | 
| Number of participants with adverse events (AEs) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results. | Up to 3 Years | 
| Plasma or serum concentrations of tislelizumab |  | Up to 30 days after last dose | 
| Plasma or serum concentrations of BGB-A445 |  | Up to 30 days after last dose | 
| Plasma or serum concentrations of LBL-007 |  | Up to 30 days after last dose | 
| Number of participants with anti-drug antibodies (ADAs) to tislelizumab |  | Up to 30 days after last dose | 
| Number of participants with anti-drug antibodies (ADAs) to LBL-007 |  | Up to 30 days after last dose | 
| Number of participants with anti-drug antibodies (ADAs) to BGB-A445 |  | Up to 30 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, programmed cell death protein-1, PD-L1 Low Tumors, PD-L1 Negative Tumors, PD-L1 High Tumors, Metastatic Non-Small Cell Lung Cancer, NSCLC