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

• ClinicalTrials.gov Identifier: NCT05635708
• Recruitment Status: Recruiting
• First Posted: December 2, 2022
• Last Update Posted: April 25, 2024
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: November 23, 2022
• First Posted Date: December 2, 2022
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: March 7, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2022)

Confirmed overall response rate (ORR) [ Time Frame: Up to 3 Years ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 5, 2024)

• Progression-free survival (PFS) [ Time Frame: Up to 3 Years ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 3 Years ]
  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
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 3 Years ]
  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
• Disease Control Rate (DCR) [ Time Frame: Up to 3 Years ]
  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
• Number of participants with adverse events (AEs) [ Time Frame: Up to 3 Years ]
  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.
• Plasma or serum concentrations of tislelizumab [ Time Frame: Up to 30 days after last dose ]
• Plasma or serum concentrations of BGB-A445 [ Time Frame: Up to 30 days after last dose ]
• Plasma or serum concentrations of LBL-007 [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to tislelizumab [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to LBL-007 [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to BGB-A445 [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to BGB-15025 [ Time Frame: Up to 30 days after last dose ]

Original Secondary Outcome Measures (submitted: November 23, 2022)

• Progression-free survival (PFS) [ Time Frame: Up to 3 Years ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 3 Years ]
  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
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 3 Years ]
  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
• Disease Control Rate (DCR) [ Time Frame: Up to 3 Years ]
  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
• Number of participants with adverse events (AEs) [ Time Frame: Up to 3 Years ]
  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.
• Plasma or serum concentrations of tislelizumab [ Time Frame: Up to 30 days after last dose ]
• Plasma or serum concentrations of BGB-A445 [ Time Frame: Up to 30 days after last dose ]
• Plasma or serum concentrations of LBL-007 [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to tislelizumab [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to LBL-007 [ Time Frame: Up to 30 days after last dose ]
• Number of participants with anti-drug antibodies (ADAs) to BGB-A445 [ Time Frame: Up to 30 days after last dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer
• Official Title: 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
• Brief Summary: 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%).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-small Cell Lung Cancer
• Metastatic Non-small Cell Lung Cancer

Intervention

• Drug: Tislelizumab
  Administered by intravenous infusion
• Drug: BGB-A445
  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
• Drug: BGB-15025
  Administered Orally

Study Arms

• Experimental: Sub-study 1: Experimental Arm 1A
  Tislelizumab + BGB-A445
  Interventions:

  • Drug: Tislelizumab
  • Drug: BGB-A445
• Experimental: Sub-study 1: Experimental Arm 2A
  Tislelizumab + LBL-007
  Interventions:

  • Drug: Tislelizumab
  • Drug: LBL-007
• Experimental: Sub-study 1: Experimental Arm 3A
  Tislelizumab + BGB-15025
  Interventions:

  • Drug: Tislelizumab
  • Drug: BGB-15025
• Experimental: Sub-study 1: Reference Arm Tislelizumab alone
  Tislelizumab alone
  Intervention: Drug: Tislelizumab
• Experimental: Sub-study 2: Experimental Arm 1B
  Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
  Interventions:

  • Drug: Tislelizumab
  • Drug: BGB-A445
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: pemetrexed
  • Drug: Paclitaxel
  • Drug: Nab paclitaxel
• Experimental: Sub-study 2: Experimental Arm 2B
  Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
  Interventions:

  • Drug: Tislelizumab
  • Drug: LBL-007
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: pemetrexed
  • Drug: Paclitaxel
  • Drug: Nab paclitaxel
• Experimental: Sub-study 2: Experimental Arm 3B
  Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
  Interventions:

  • Drug: Tislelizumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: pemetrexed
  • Drug: Paclitaxel
  • Drug: Nab paclitaxel
  • Drug: BGB-15025
• Active Comparator: Sub-study 2: Reference Arm
  Tislelizumab + investigator's choice of histology-appropriate chemotherapy
  Interventions:

  • Drug: Tislelizumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: pemetrexed
  • Drug: Paclitaxel
  • Drug: Nab paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 5, 2024): 400
• Original Estimated Enrollment (submitted: November 23, 2022): 300
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BeiGene; +1-877-828-5568; clinicaltrials@beigene.com

• Listed Location Countries: Australia, Brazil, Canada, China, Georgia, Italy, Korea, Republic of, Malaysia, Moldova, Republic of, Romania, Singapore, Spain, Thailand, United States

Administrative Information

• NCT Number: NCT05635708
• Other Study ID Numbers: BGB-LC-201; CTR20230892 ( Other Identifier: ChinaDrugTrials )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; BeiGene

• PRS Account: BeiGene
• Verification Date: April 2024