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

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

This study was conducted to evaluate the preliminary effectiveness and safety of treatment with tislelizumab alone and in combination with other investigational agents prior to surgery (neoadjuvant treatment) in adults with non-small cell lung cancer (NSCLC) that is able to be removed by surgery.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Ociperlimab; Drug: Alcestobart; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: Paclitaxel

Detailed Description

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 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.

The study consisted of a neoadjuvant treatment phase (2 - 4 cycles of treatment), a surgery phase and a follow-up phase.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Wuhu, Anhui, China, 241001
      • The First Affiliated Hospital of Wannan Medical College
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510140
      • The First Affiliated Hospital of Guangzhou Medical Universitydatansha Hospital)
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The Tumor Hospital Affiliated to Guangxi Medical University
  • Henan
    • Anyang, Henan, China, 455001
      • Anyang Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 332000
      • The First Affiliated Hospital of Nanchang University Branch Xianghu
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
    • Shanghai, Shanghai Municipality, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Zhejiang
    • Ningbo, Zhejiang, China, 315000
      • Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 co-stimulation 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 epidermal growth factor receptor (EGFR) sensitizing mutations and/or anaplastic lymphoma kinase (ALK) rearrangement

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1A: Tislelizumab Monotherapy; Participants with tumor programmed death protein ligand-1 (PD-L1) expression ≥ 50% received 200 mg tislelizumab intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.	Drug: Tislelizumab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A317; Tevimbra
Experimental: Arm 1B: Tislelizumab + Ociperlimab; Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 900 mg ociperlimab intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.	Drug: Tislelizumab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A317; Tevimbra; Drug: Ociperlimab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A1217
Experimental: Arm 1C: Alcestobart + Tislelizumab; Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 600 mg alcestobart intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.	Drug: Tislelizumab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A317; Tevimbra; Drug: Alcestobart; Administered as an intravenous infusion once every 3 weeks; Other Names: LBL-007
Experimental: Arm 2A: Tislelizumab and Chemotherapy; Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.	Drug: Tislelizumab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A317; Tevimbra; Drug: Cisplatin; 75 mg/m^2 administered as an intravenous infusion once every 3 weeks; Drug: Carboplatin; Administered as an intravenous infusion once every 3 weeks at an area under the curve (AUC) of 5 mg/mL/min; Drug: Pemetrexed; 500 mg/m^2 administered as an intravenous infusion once every 3 weeks in participants with non-squamous NSCLC; Drug: Paclitaxel; 175 mg/m^2 administered as an intravenous infusion once every 3 weeks in participants with squamous NSCLC
Experimental: Arm 2C: Alcestobart + Tislelizumab + Chemotherapy; Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.	Drug: Tislelizumab; Administered as an intravenous infusion once every 3 weeks; Other Names: BGB-A317; Tevimbra; Drug: Alcestobart; Administered as an intravenous infusion once every 3 weeks; Other Names: LBL-007; Drug: Cisplatin; 75 mg/m^2 administered as an intravenous infusion once every 3 weeks; Drug: Carboplatin; Administered as an intravenous infusion once every 3 weeks at an area under the curve (AUC) of 5 mg/mL/min; Drug: Pemetrexed; 500 mg/m^2 administered as an intravenous infusion once every 3 weeks in participants with non-squamous NSCLC; Drug: Paclitaxel; 175 mg/m^2 administered as an intravenous infusion once every 3 weeks in participants with squamous NSCLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) Rate	Tumor tissue and lymph node tissue obtained from surgical resection were sent to a central laboratory according to study pathology manuals for pathological response analysis. MPR rate is defined as the percentage 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). Participants without surgery or pathological results were considered non-responders.	At the time of surgery, approximately Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR)	Pathological complete response is defined as the percentage of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR. Participants without surgery or pathological results were considered as non-responders.	At the time of surgery, approximately Week 16
Event-free Survival (EFS)	EFS is defined as the time from randomization until any of the following events, whichever occurred 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. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. Median EFS was estimated using Kaplan-Meier methodology.	From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
Event-free Survival Rate	Event-free survival rate is defined as the percentage of participants with none of the following events: radiographic disease progression that precludes definitive surgery, local or distant recurrence as assessed by investigator per RECIST v1.1, or death due to any cause. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. EFS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.	12 months and 24 months after randomization
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology.	From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
Overall Survival Rate	Overall survival rate is defined as the percentage of participants who were still alive at the analysis time points. OS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.	12 months and 24 months after randomization
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 occurred first. Median DFS was estimated using Kaplan-Meier methodology.	From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
Disease-free Survival Rate	Disease-free survival rate is defined as the percentage of participants with none of the following events: Local or distant recurrence as assessed by the investigator per RECIST v1.1, or death due to any cause. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. DFS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.	12 months and 24 months after randomization
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required hospitalization or prolongation of existing hospitalization; Resulted in disability/incapacity; Was a congenital anomaly/birth defect; Was considered a significant medical AE by the investigator or sponsor based on medical judgement (eg, may have jeopardized the participant or may require medical/surgical intervention to prevent one of the outcomes listed above). Immune-mediated adverse events (imAEs) are autoimmune-mediated complications that may develop in response to immunotherapeutic agents. Immune-mediated AEs were collected from the date of first dose of study drug to 90 days after the last dose of study drug, regardless of whether the participant started a new anticancer therapy or prespecified adjuvant treatment. imAEs were identified by the investigator based on a standard process defined in the Protocol.	From first dose of study drug until 30 days after last dose or new anticancer treatment, whichever occurred first, or up to 90 days after the last dose for imAEs; maximum duration of treatment was 14 weeks.
Feasibility of Surgery	Feasibility of surgery was assessed by the number of participants who underwent surgical resection (surgery) within 6 weeks of last dose of study drug, had delayed or canceled surgery, the approach of surgery, duration of surgery (see next outcome measure) ,and the number of participants who underwent an exploratory thoracotomy, a surgical procedure in which a cut is made between the ribs to see and reach the lungs or other organs in the chest or thorax. Exploratory thoracotomy was not counted as surgery.	At the time of surgery, approximately Week 16
Duration of Surgery	The duration of surgery is defined as the time interval from the start of the surgical procedure to its completion.	Approximately Week 16

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2023
• Primary Completion (Actual): December 13, 2024
• Study Completion (Actual): January 23, 2025

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; tislelizumab
• Other Study ID Numbers: BGB-LC-202; CTR20222760 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Begene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

Beigene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for Beigene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No