Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA non-small cell lung cancer (NSCLC). The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population.

Official Title
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A Randomized, Open-Label, Multicenter, Phase 2, Umbrella Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations With and Without Chemotherapy as Neoadjuvant Treatment in Chinese Patients With Resectable Stage II to IIIA Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Ociperlimab
* Drug: LBL-007
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Pemetrexed
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer [NSCLC] staging system) Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization Provide formalin-fixed paraffin-embedded block (preferred) or at least 15 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening Exclusion Criteria: Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-cell immunoglobulin and ITIM domain (TIGIT), anti-lymphocyte activation gene-3 (LAG-3), or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways Has mixed small cell lung cancer Participants with large cell neuroendocrine carcinoma (LCNEC) The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease Known EGFR sensitizing mutations and/or ALK rearrangement 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1A: Tislelizumab Monotherapy<br>Tislelizumab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;|
| Experimental: Arm 1B: Tislelizumab and Ociperlimab<br>Tislelizumab + ociperlimab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Ociperlimab<br>* Administered as an intravenous infusion<br>* Other names: BGB-A1217;|
| Experimental: Arm 1C: Tislelizumab and LBL-007<br>Tislelizumab + LBL-007 on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>|
| Experimental: Arm 2A: Tislelizumab and Chemotherapy<br>Tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include: Cisplatin/carboplatin + pemetrexed (nonsquamous) Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>|
| Experimental: Arm 2C: LBL-007 and Tislelizumab and Chemotherapy<br>LBL-007 + tislelizumab + chemotherapy on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days); Platinum-based doublet chemotherapy options may include: Cisplatin/carboplatin + pemetrexed (nonsquamous) Cisplatin/carboplatin + paclitaxel (squamous) | Drug: Tislelizumab<br>* Administered as an intravenous infusion<br>* Other names: Tevimbra;Drug: LBL-007<br>* Administered as an intravenous infusion<br>Drug: Cisplatin<br>* Administered as an intravenous infusion<br>Drug: Carboplatin<br>* Administered as an intravenous infusion<br>Drug: Pemetrexed<br>* Administered as an intravenous infusion<br>Drug: Paclitaxel<br>* Administered as an intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) | MPR is defined as the proportion of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR) | Up to approximately 18 weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) | pCR is defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR | Up to approximately 18 weeks after first dose | 
| Event-free survival (EFS) | EFS is defined as the time from randomization until any of the following events, whichever occurs first: radiographic disease progression that precludes definitive surgery, local or distant recurrence, as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause | Up to approximately 2 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 2 years | 
| Disease-free survival (DFS) | DFS is defined as the time from the first date of no disease (ie, participants who underwent margin-negative [R0] resection) to local or distant recurrence, as assessed by the investigator according to RECIST v1.1, or death due to any cause, whichever occurs first | Up to approximately 2 years | 
| Number of participants with adverse events | Number of participants with treatment-emergent adverse events, including serious adverse events and immune-mediated adverse events (imAEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 | Up to approximately 2 years | 
| Proportion of participants who undergo surgical resection | Proportion of participants who undergo surgical resection within a scheduled period after receiving any dose of investigational agents, delayed or canceled surgery, duration of surgery and surgical approach | Up to approximately 18 weeks after first dose | 
| Serum or plasma concentrations of investigational agents |  | Up to 30 days after last dose | 
| Number of participants with anti-drug antibodies (ADAs) |  | Up to 30 days after last dose |