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

Registration Number
NCT05577702
Lead Sponsor
BeiGene
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
121
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1B: Tislelizumab and OciperlimabOciperlimabTislelizumab + ociperlimab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days)
Arm 1C: Tislelizumab and LBL-007LBL-007Tislelizumab + LBL-007 on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyLBL-007LBL-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)
Arm 1A: Tislelizumab MonotherapyTislelizumabTislelizumab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days)
Arm 1B: Tislelizumab and OciperlimabTislelizumabTislelizumab + ociperlimab on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days)
Arm 2A: Tislelizumab and ChemotherapyCisplatinTislelizumab + 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)
Arm 1C: Tislelizumab and LBL-007TislelizumabTislelizumab + LBL-007 on a 3-week cycle for 2 to 4 cycles, followed by surgical resection (each cycle is 21 days)
Arm 2A: Tislelizumab and ChemotherapyPemetrexedTislelizumab + 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)
Arm 2A: Tislelizumab and ChemotherapyTislelizumabTislelizumab + 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)
Arm 2A: Tislelizumab and ChemotherapyCarboplatinTislelizumab + 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)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyPemetrexedLBL-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)
Arm 2A: Tislelizumab and ChemotherapyPaclitaxelTislelizumab + 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)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyTislelizumabLBL-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)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyCisplatinLBL-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)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyCarboplatinLBL-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)
Arm 2C: LBL-007 and Tislelizumab and ChemotherapyPaclitaxelLBL-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)
Primary Outcome Measures
NameTimeMethod
Major Pathological Response (MPR)Up to approximately 18 weeks after first dose

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)

Secondary Outcome Measures
NameTimeMethod
Pathological complete response (pCR)Up to approximately 18 weeks after first dose

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

Event-free survival (EFS)Up to approximately 2 years

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

Overall survival (OS)Up to approximately 2 years

OS is defined as the time from the date of randomization to the date of death due to any cause

Disease-free survival (DFS)Up to approximately 2 years

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

Number of participants with adverse eventsUp to approximately 2 years

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

Proportion of participants who undergo surgical resectionUp to approximately 18 weeks after first dose

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

Trial Locations

Locations (14)

Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital)

🇨🇳

Ningbo, Zhejiang, China

The First Affiliated Hospital of Wannan Medical College

🇨🇳

Wuhu, Anhui, China

Beijing Cancer Hospital

🇨🇳

Beijing, Beijing, China

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, Fujian, China

The First Affiliated Hospital of Guangzhou Medical Universitydatansha Hospital)

🇨🇳

Guangzhou, Guangdong, China

The Tumor Hospital Affiliated to Guangxi Medical University

🇨🇳

Nanning, Guangxi, China

Anyang Cancer Hospital

🇨🇳

Anyang, Henan, China

Hubei Cancer Hospital

🇨🇳

Wuhan, Hubei, China

Liaoning Cancer Hospital and Institute

🇨🇳

Shenyang, Liaoning, China

Shandong Cancer Hospital

🇨🇳

Jinan, Shandong, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

The First Affiliated Hospital of Nanchang University Branch Xianghu

🇨🇳

Nanchang, Jiangxi, China

Shanghai Pulmonary Hospital

🇨🇳

Shanghai, Shanghai, China

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