A Study of BGB-A445 in Combination With Other Investigational Agents in Participants With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the anti-tumor activity of BGB-A445 plus investigational agents in participants with non-small cell lung cancer (NSCLC)

Detailed Description
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This study will test whether BGB-A445 in combination with other agents can help treat participants with non-small cell lung cancer (NSCLC) who were already treated with other anticancer agents, including anti-programmed cell death protein-1 (anti-PD-1) and anti-programmed cell death protein ligand-1 (anti-PD-L1) antibodies. The main goal of this study is to see if BGB-A445 can increase participant response to treatment, also called the overall response rate Only a portion of patients with advanced solid tumors have a durable response to currently available treatments. This represents an unmet medical need to develop improved therapeutic options. Combining targeted vascular therapies with immunotherapies might improve outcomes for these patients. This study is designed as a proof of concept to show that BGB-A445-based combination treatment may be able to improve responses and clinical benefit in patients with NSCLC. Stage 1 of the study will take place in China and the Asia Pacific region and Stage 2 will be expanded to take place worldwide. The overall time to participate in this study is approximately 3 years. Treatments will continue until participants experience no benefits, too many side effects, or withdraw consent.

Official Title
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A Phase 2, Open-label, Randomized, Multi-arm Study of BGB-A445 in Combination With Investigational Agents in Non-Small Cell Lung Cancer Patients Previously Treated With Anti-PD-(L)1 Antibody

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: BGB-A445
* Drug: Docetaxel
* Drug: Tislelizumab
* Drug: Sitravatinib
* Drug: Ramucirumab
* Drug: Selected Interventions
* Drug: BGB-15025


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or metastatic NSCLC (nonsquamous or squamous) that is histologically or cytologically confirmed Participants who have received no more than 2 lines of prior systemic therapies which must include anti-programmed cell death protein ligand-1 (anti-PD-L1) anti-PD-(L)1 treatment At least 1 measurable lesion as defined per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Adequate organ function as indicated by laboratory values during screening Exclusion Criteria: With mixed small cell lung cancer Has received prior therapy targeting OX40 or any other T-cell agonists Has received prior therapy containing docetaxel and/or ramucirumab for advanced or metastatic NSCLC Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before the first dose of study drug(s) Active leptomeningeal disease or uncontrolled and untreated brain metastasis NOTE: Other 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: Stage 1: BGB-A445 + Docetaxel<br>BGB-A445 + Docetaxel | Drug: BGB-A445<br>* Administered intravenously at protocol defined dose<br>Drug: Docetaxel<br>* 75 milligrams per square meter (mg/m^2) administered intravenously<br>|
| Experimental: Stage 1: BGB-A445 + Tislelizumab + Sitravatinib<br>BGB-A445 + tislelizumab + Sitravatinib | Drug: BGB-A445<br>* Administered intravenously at protocol defined dose<br>Drug: Tislelizumab<br>* Administered intravenously at protocol defined dose<br>* Other names: BGB-A317;Drug: Sitravatinib<br>* Administered orally at protocol defined dose<br>|
| Experimental: Stage 1: BGB-A445 + BGB-15025<br>BGB-A445 + BGB-15025 | Drug: BGB-A445<br>* Administered intravenously at protocol defined dose<br>Drug: BGB-15025<br>* Administered orally at protocol defined dose<br>|
| Experimental: Stage 2: BGB-A445 + selected investigational agent(s) from Stage 1<br>BGB-A445 + selected investigational agent(s) from Stage 1 (either Docetaxel, Tislelizumab + Sitravatinib or BGB-15025) | Drug: BGB-A445<br>* Administered intravenously at protocol defined dose<br>Drug: Docetaxel<br>* 75 milligrams per square meter (mg/m^2) administered intravenously<br>Drug: Tislelizumab<br>* Administered intravenously at protocol defined dose<br>* Other names: BGB-A317;Drug: Sitravatinib<br>* Administered orally at protocol defined dose<br>Drug: Selected Interventions<br>* Administered at protocol defined dose<br>Drug: BGB-15025<br>* Administered orally at protocol defined dose<br>|
| Other: Docetaxel + Ramucirumab<br>Reference to Stage 2: Ramucirumab + Docetaxel | Drug: Docetaxel<br>* 75 milligrams per square meter (mg/m^2) administered intravenously<br>Drug: Ramucirumab<br>* 10 mg/kg administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate (ORR) is defined as the percentage of participants with best overall response (BOR) of a complete response (CR) or partial response (PRas assessed by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1. ). | Up to Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | Up to Approximately 3 years | 
| Duration of Response (DOR) | DOR is defined as the time from the first determination of an objective response as assessed by the investigator per RECIST v1 until the first documentation of progression or death, whichever comes first | Up to Approximately 3 years | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants with BOR of a CR, PR, or stable disease. | Up to Approximately 3 years | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with BOR of a CR, PR, or stable disease lasting ≥ 24 weeks | Up to Approximately 3 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or death due to any cause, whichever occurs first | Up to Approximately 3 years | 
| Overall Survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause | Up to Approximately 3 years | 
| Plasma and Serum Concentrations of BGB-A445 and Investigational Agents |  | Days 1, 8, and 15 of Cycle 1 and days 1 and 8 of Cycle 2, and Day 1 of all subsequent Cycles and End of Study Visit - Up to approximately 3 years (each cycle 21 days) | 
| Number of participants with Ant-Drug Antibodies to BGB-A445 and Investigational Agents |  | Up to Approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-L1, NSCLC