A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer

Master Protocol: A Phase 2, Open-label, Multi-arm Study of Tislelizumab in Combination With Investigational Agents With or Without Chemotherapy in Patients With Previously Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer

The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without chemotherapy. This study is structured as a master protocol with separate sub- studies. Sub-study 1 includes participants with non-small cell lung cancer (NSCLC) with high programmed cell death protein ligand-1 (PD-L1) expression (≥ 50%), and Sub-study 2 includes participants with NSCLC with low or negative (PD-L1) expression (< 50%).

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: BGB-A445; Drug: LBL-007; Drug: Carboplatin; Drug: Cisplatin; Drug: pemetrexed; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: BGB-15025

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: +1-877-828-5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris Obrien Lifehouse
    • Frenchs Forest, New South Wales, Australia, 2086
      • Recruiting
      • Northern Beaches Hospital
    • Port Macquarie, New South Wales, Australia, 2444
      • Recruiting
      • Port Macquarie Base Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research
    • Subiaco, Western Australia, Australia, 6008
      • Recruiting
      • St John of God Health Care
• Brazil
  • Barretos, Brazil, 14784-400
    • Recruiting
    • Hospital de Amor Barretos
  • Londrina, Brazil, 86015-520
    • Recruiting
    • Hospital Do Cancer de Londrina
  • Porto Alegre, Brazil, 90850-170
    • Recruiting
    • Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
  • Sao Jose do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • Sao Paulo, Brazil, 01246-000
    • Recruiting
    • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G1Z2
      • Recruiting
      • Cross Cancer Institute
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Hospital of Anhui medical university
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian cancer hospital
  • Hebei
    • Baoding, Hebei, China, 071000
      • Recruiting
      • Affiliated Hospital of Hebei University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei Cancer Hospital
  • Jiangsu
    • Nantong, Jiangsu, China, 226000
      • Recruiting
      • Nantong Tumor Hospital Branch North
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 332000
      • Recruiting
      • The First Affiliated Hospital of Nanchang University Branch Xianghu
  • Shandong
    • Jining, Shandong, China, 272000
      • Recruiting
      • Jining No Peoples Hospital
    • Linyi, Shandong, China, 276000
      • Recruiting
      • Linyi Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Affiliated Zhongshan Hospital of Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Shanxi Provincial Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Taizhou, Zhejiang, China, 317000
      • Recruiting
      • Taizhou Hospital of Zhejiang
• Georgia
  • Tbilisi, Georgia, 0112
    • Recruiting
    • Arensia Exploratory Medicine Llc
• Italy
  • Roma, Italy, 00144
    • Recruiting
    • Regina Elena, Istituto Nazionale Dei Tumori, Ifo, Irccs
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche Di Verona
• Korea, Republic of
  • Chungcheongbukdo
    • Cheongjusi, Chungcheongbukdo, Korea, Republic of, 28644
      • Recruiting
      • Chungbuk National University Hospital
  • Gyeonggido
    • Goyangsi, Gyeonggido, Korea, Republic of, 10408
      • Recruiting
      • National Cancer Center
    • Seongnamsi, Gyeonggido, Korea, Republic of, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
    • Suwonsi, Gyeonggido, Korea, Republic of, 16247
      • Recruiting
      • The Catholic University of Korea, St Vincents Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Recruiting
      • Samsung Medical Center
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Recruiting
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Recruiting
      • Asan Medical Center
• Malaysia
  • Georgetown, Malaysia, 10450
    • Recruiting
    • Pulau Pinang Hospital
  • Johor Bahru, Malaysia, 81100
    • Recruiting
    • Sultan Ismail Hospital
  • Kuantan, Malaysia, 25100
    • Recruiting
    • Tengku Ampuan Afzan Hospital
  • Kuching, Malaysia, 93586
    • Recruiting
    • Sarawak General Hospital
  • Petaling Jaya, Malaysia, 46050
    • Recruiting
    • Beacon Hospital
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Recruiting
    • The Institute of Oncology, Arensia Exploratory Medicine
• Romania
  • ClujNapoca, Romania, 400015
    • Recruiting
    • Arensia Research Clinic At the Oncology Institute Prof Dr Ion Chiricu
• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • National Cancer Centre Singapore
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall Dhebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario de Octubre
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
• Thailand
  • Hat Yai, Thailand, 90110
    • Recruiting
    • Songklanagarind Hospital (Prince of Songkhla University)
  • Muang, Thailand, 40002
    • Recruiting
    • Srinagarind Hospital (Khon Kaen University)
  • Muang, Thailand, 50200
    • Recruiting
    • Maharaj Nakorn Chiang Mai Hospital (Chiang Mai University)
  • Ongkharak, Thailand, 26120
    • Recruiting
    • Hrh Princess Maha Chakri Sirindhorn Medical Center (Srinakharinwirot University)
• United States
  • California
    • Encinitas, California, United States, 92024
      • Recruiting
      • California Cancer Associates For Research and Excellence, Ccare Encinitas
    • Los Angeles, California, United States, 90067
      • Recruiting
      • Valkyrie Clinical Trials
    • San Marcos, California, United States, 92069
      • Recruiting
      • California Cancer Associates For Research and Excellence, Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center Mskcc
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225-9722
      • Recruiting
      • Oncology and Hematology Care Clinic Westside
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed NSCLC (nonsquamous or squamous) that is locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC.
2. No prior systemic treatment given as primary therapy for metastatic NSCLC. Prior adjuvant/neoadjuvant chemotherapy or definitive chemoradiation/adjuvant radiotherapy for locally advanced disease is allowed provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months before randomization/enrollment.
3. Evaluable tumor PD-L1 expression as determined by a local laboratory or by central laboratory on archival tumor tissue or fresh biopsy. Patients with unknown PD-L1 expression will not be eligible for this study.
4. At least 1 measurable lesion as defined per RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria:

1. Has mixed small cell lung cancer.
2. Participants with known actionable mutations (including but not limited to EGFR, ALK, BRAF, RET, and ROSI mutations) for which a targeted therapy is available per local standard of care.
3. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, anti-LAG-3 or any other antibody or drug targeting T-cell costimulation or immune checkpoint pathways. Note: Patients who received prior neoadjuvant, adjuvant or immuno-oncology therapies targeting PD-1 or PD-L1 in consolidation are eligible, if there has been a treatment-free interval of ≥ 6 months from last dose of immuno-oncology therapy prior to radiologic recurrence of disease.
4. Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before randomization/enrollment.
5. Active leptomeningeal disease or uncontrolled, untreated brain metastasis, or active autoimmune diseases.

NOTE: Other protocol and sub-study protocol defined 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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub-study 1: Experimental Arm 1A; Tislelizumab + BGB-A445	Drug: Tislelizumab; Administered by intravenous infusion; Drug: BGB-A445; Administered by intravenous infusion
Experimental: Sub-study 1: Experimental Arm 2A; Tislelizumab + LBL-007	Drug: Tislelizumab; Administered by intravenous infusion; Drug: LBL-007; Administered by intravenous infusion
Active Comparator: Sub-study 2: Reference Arm; Tislelizumab + investigator's choice of histology-appropriate chemotherapy	Drug: Tislelizumab; Administered by intravenous infusion; Drug: Carboplatin; Investigator's choice; administered by intravenous infusion; Drug: Cisplatin; Investigator's choice; administered by intravenous infusion; Drug: pemetrexed; Investigator's choice; administered by intravenous infusion; Drug: Paclitaxel; Investigator's choice; administered by intravenous infusion; Drug: Nab paclitaxel; Investigator's choice; administered by intravenous infusion
Experimental: Sub-study 1: Experimental Arm 3A; Tislelizumab + BGB-15025	Drug: Tislelizumab; Administered by intravenous infusion; Drug: BGB-15025; Administered Orally
Experimental: Sub-study 1: Reference Arm Tislelizumab alone; Tislelizumab alone	Drug: Tislelizumab; Administered by intravenous infusion
Experimental: Sub-study 2: Experimental Arm 1B; Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445	Drug: Tislelizumab; Administered by intravenous infusion; Drug: BGB-A445; Administered by intravenous infusion; Drug: Carboplatin; Investigator's choice; administered by intravenous infusion; Drug: Cisplatin; Investigator's choice; administered by intravenous infusion; Drug: pemetrexed; Investigator's choice; administered by intravenous infusion; Drug: Paclitaxel; Investigator's choice; administered by intravenous infusion; Drug: Nab paclitaxel; Investigator's choice; administered by intravenous infusion
Experimental: Sub-study 2: Experimental Arm 2B; Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007	Drug: Tislelizumab; Administered by intravenous infusion; Drug: LBL-007; Administered by intravenous infusion; Drug: Carboplatin; Investigator's choice; administered by intravenous infusion; Drug: Cisplatin; Investigator's choice; administered by intravenous infusion; Drug: pemetrexed; Investigator's choice; administered by intravenous infusion; Drug: Paclitaxel; Investigator's choice; administered by intravenous infusion; Drug: Nab paclitaxel; Investigator's choice; administered by intravenous infusion
Experimental: Sub-study 2: Experimental Arm 3B; Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025	Drug: Tislelizumab; Administered by intravenous infusion; Drug: Carboplatin; Investigator's choice; administered by intravenous infusion; Drug: Cisplatin; Investigator's choice; administered by intravenous infusion; Drug: pemetrexed; Investigator's choice; administered by intravenous infusion; Drug: Paclitaxel; Investigator's choice; administered by intravenous infusion; Drug: Nab paclitaxel; Investigator's choice; administered by intravenous infusion; Drug: BGB-15025; Administered Orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed overall response rate (ORR)	ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1	Up to 3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the time from date of randomization, or the first dose for safety lead-in participants , until first documentation of progression or death, whichever comes first, as assessed by the investigator using RECIST v1.	Up to 3 Years
Duration of Response (DOR)	DOR is defined as the time from the first determination of a confirmed response per RECIST v1.1 until the first documentation of progression or death, whichever comes first as assessed by the investigator	Up to 3 Years
Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with a best overall response of a complete response, partial response, or durable stable disease, as assessed by the investigator using RECIST v1.1	Up to 3 Years
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with a best overall response of complete response, partial response, or stable disease, as assessed by the investigator using RECIST v1.1	Up to 3 Years
Number of participants with adverse events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results.	Up to 3 Years
Plasma or serum concentrations of tislelizumab		Up to 30 days after last dose
Plasma or serum concentrations of BGB-A445		Up to 30 days after last dose
Plasma or serum concentrations of LBL-007		Up to 30 days after last dose
Number of participants with anti-drug antibodies (ADAs) to tislelizumab		Up to 30 days after last dose
Number of participants with anti-drug antibodies (ADAs) to LBL-007		Up to 30 days after last dose
Number of participants with anti-drug antibodies (ADAs) to BGB-A445		Up to 30 days after last dose
Number of participants with anti-drug antibodies (ADAs) to BGB-15025		Up to 30 days after last dose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Non-small Cell Lung Cancer; Metastatic Non-Small Cell Lung Cancer; programmed cell death protein-1; PD-L1 Low Tumors; PD-L1 Negative Tumors; PD-L1 High Tumors
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Pemetrexed; Tislelizumab
• Other Study ID Numbers: BGB-LC-201; CTR20230892 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No