Study to Evaluate the Bioavailability of Tislelizumab Via Subcutaneous Injection in First-Line Treatment of Participants With Advanced or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase 1 clinical study to evaluate the bioavailability of tislelizumab subcutaneous (SC) injection in the first-line treatment of participants with advanced or metastatic non-small cell lung cancer (NSCLC). This clinical study will be divided into 2 parts: dose/injection site exploration (Part 1) and dose expansion (Part 2).

Official Title
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Phase 1 Study to Evaluate the Bioavailability of Tislelizumab Via Subcutaneous Injection in the First-Line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab IV
* Drug: Tislelizumab SC
* Drug: Histology-Based Chemotherapy Doublet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to sign a written consent form, understand, and agree to comply with requirements of the study. Documented locally advanced or recurrent NSCLC that is not eligible for curative surgery and/or definitive radiotherapy, with or without chemotherapy, or metastatic non-squamous or squamous NSCLC. No prior systemic treatment for advanced or metastatic NSCLC, including but not limited to chemotherapy or targeted therapy. At least one measurable lesion as assessed by RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) PS ≤ 1. Adequate organ function as indicated by laboratory tests. Exclusion Criteria: Participants diagnosed with NSCLC that harbor a driver mutation (eg, EGFR-sensitizing mutation, ALK fusion oncogene, and BRAF V600E mutation or ROS1 mutation). Participant has received any Chinese herbal medicine or Chinese patent medicines used to control cancer within 14 days before first dose of study drug. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. Active autoimmune diseases or history of autoimmune diseases that may relapse. Any cancer ≤ 5 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, localized prostate cancer, carcinoma in situ of the cervix or breast). Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drug. 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose/Injection Site Exploration<br>Different injection sites will be evaluated; participants will receive tislelizumab in predefined administration sequences plus histology-based chemotherapy consisting of either cisplatin/carboplatin and pemetrexed or carboplatin and paclitaxel/nab-paclitaxel depending on the cancer subtype. | Drug: Tislelizumab IV<br>* Planned doses will be administered intravenously.<br>* Other names: BGB-A317 IV;Drug: Tislelizumab SC<br>* Planned doses will be administered via subcutaneous injection.<br>* Other names: BGB-A317 SC;Drug: Histology-Based Chemotherapy Doublet<br>* Chemotherapy Doublet 1: Cisplatin/carboplatin + pemetrexed. Chemotherapy Doublet 2: Carboplatin + paclitaxel/nab-paclitaxel. Choice of histology-based induction chemotherapy doublet will be determined by the investigator and will be administered at standard doses intravenously.<br>|
| Experimental: Part 2: Dose Expansion<br>The recommended dose of tislelizumab SC determined from Part 1 plus histology-based chemotherapy consisting of either cisplatin/carboplatin and pemetrexed or carboplatin and paclitaxel/nab-paclitaxel depending on the cancer subtype will be evaluated. | Drug: Tislelizumab SC<br>* Planned doses will be administered via subcutaneous injection.<br>* Other names: BGB-A317 SC;Drug: Histology-Based Chemotherapy Doublet<br>* Chemotherapy Doublet 1: Cisplatin/carboplatin + pemetrexed. Chemotherapy Doublet 2: Carboplatin + paclitaxel/nab-paclitaxel. Choice of histology-based induction chemotherapy doublet will be determined by the investigator and will be administered at standard doses intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and 2: Area under the concentration-time curve (AUC) of Tislelizumab SC |  | Up to approximately 3.5 months | 
| Part 1 and 2: Concentration at the end of dosing interval (Ctrough) of Tislelizumab SC |  | Up to approximately 3.5 months | 
| Part 1: Bioavailability of Tislelizumab SC |  | Up to approximately 2 months | 
| Part 2: Maximum observed plasma concentration (Cmax) of Tislelizumab SC |  | Up to approximately 3.5 months | 
| Part 2: Accumulation ratio (Rac) of Tislelizumab SC |  | Up to approximately 3.5 months | 
| Part 2: Elimination half-life (t1/2) of Tislelizumab SC |  | Up to approximately 3.5 months | 
| Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with AEs and SAEs and laboratory abnormalities, reported during the AE reporting period and characterized by type, frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE v5.0]), timing, seriousness, and relationship to study therapy. | Up to approximately 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum observed concentration (Cmax) of Tislelizumab SC |  | Up to approximately 2 months | 
| Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with AEs and SAEs and laboratory abnormalities, reported during the AE reporting period and characterized by type, frequency, severity (as graded by NCI-CTCAE v5.0), timing, seriousness, and relationship to study therapy. | Up to approximately 27 months | 
| Part 1 and 2: Number of Participants with Anti-Tislelizumab Antibodies |  | Up to 25 months | 
| Part 2: Overall Response Rate (ORR) of Tislelizumab SC | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as determined from tumor assessments by investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). | Up to approximately 27 months | 
| Part 2: Duration of Response (DOR) of Tislelizumab SC | DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death due to any cause, whichever occurs first as assessed by the investigator. | Up to approximately 27 months | 
| Part 2: Progression-Free Survival (PFS) | PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death due to any cause, whichever occurs first. | Up to approximately 27 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, non-small cell lung cancer